2-芳基-喹啉-4-羧酸衍生物的合成及生物活性研究
|
摘要
2-芳基-喹啉-4-羧酸是一类具有广泛生物活性的化合物。文献曾报道该类化合物具有解热镇痛抗炎、抗氧化、抗肿瘤和抗病毒等药理作用。其中早期在临床中应用的解热镇痛药辛可芬,曾被用于痛风等疾病的治疗。目前该药与泼尼松龙联合使用治疗动物关节炎。近二十年来,针对2-芳基-喹啉-4-羧酸衍生物的设计、合成及生物活性的研究一直没有停止。本论文主要针对前期所发现该类化合物具有荧光检测和抗肿瘤等生物活性进行深入研究
近年来报道的2-芳基硼酸-喹啉-4-羧酸化合物可作为识别糖类物质的水溶性荧光探针。该化合物与糖结合后荧光强度增幅大且结构适于衍生化。本课题组前期曾以该结构为先导,设计、合成一系列二硼酸化合物,并对其针对寡糖的识别作用进行了初步研究。本论文在前期工作的基础上,发现2-芳基硼酸-喹啉-4-羧酸与儿茶酚衍生物相互结合后荧光强度大幅降低。针对这一反常现象,经过多个实验证实引起荧光强度降低的现象是由硼酸化合物引起的,且该硼酸化合物与儿茶酚的亲和力比糖类化合物高。由于该化合物与儿茶酚类物质结合后荧光强度变化与糖类物质趋势正好相反,因此也适于作为选择性识别儿茶酚类物质的荧光探针。我们还应用兔血浆替代缓冲溶液,结果证实荧光强度随儿茶酚浓度升高而显著降低,且浓度依赖性较好,因此该荧光探针可适用于在血浆等生物样本中识别儿茶酚类物质。
儿茶酚物质在体内分布广泛且发挥多种生物活性,特别是儿茶酚胺类物质(如多巴胺,左旋多巴,肾上腺素等)与体内心血管疾病和中枢神经系统疾病有重多关系。研究选择性识别儿茶酚胺类物质的荧光探针具有重要科学和实用意义。然而2-芳基硼酸-喹啉-4-羧酸化合物尽管与儿茶酚亲和力高,但对多巴胺和左旋多巴等儿茶酚胺类物质选择性却不理想。考虑到儿茶酚胺结构中存在游离氨基结构,我们结合过去研究硼酸类荧光探针的经验,在2-芳基硼酸-喹啉-4-羧酸结构中羧酸部位进行改造,引入羧酸或另一个硼酸作为第二识别位点。目标化合物在设计中不仅考虑两个识别位点的性质,还进一步考察不同长度、柔性的连接臂(Linker),以期目标化合物与儿茶酚胺类生命活性物质的亲和力和选择性。在设计、合成的47个新化合物中,目标化合物18个,所有化合物通质谱、核磁共振氢谱、碳谱或高分辨质谱确证。通过初步的荧光活性筛选发现,化合物9d对左旋多巴的亲和力是多巴胺和儿茶酚的两倍,初步实现对左旋多巴的选择性。比较目标化合物9d与其类似物的结构可以发现,喹啉母核结构4-位引入不同链长的烷基羧酸结构对于儿茶酚胺类物质的亲和力有重要影响。当链长为1个或3个碳原子时,新化合物并未显示选择性；当链长为5个碳原子时,化合物9d与左旋多巴的亲和力和选择性均有较大提高,这为今后进一步寻找选择性识别儿茶酚胺物质提供了可供借鉴的新思路。除此之外,活性筛选中还发现目标化合物10h不仅对多巴胺具有较好的选择活性,而且其发射波长(484nm)明显长于先导物2-芳基硼酸-喹啉-4-羧酸(382nm)。这为研究新型长波类水溶性荧光探针提供了新的研究手段和研究工具。
本课题组多年来从事针对组蛋白去乙酰化酶(HDACs)抑制剂的研究,并先后发表了基于四氢异喹啉和噻二唑等杂环的结构类型。根据近期发现的噻二唑类HDAC抑制剂构效关系研究结果,作为HDAC抑制剂表面识别区域的噻二唑与苯环直接相连的化合物活性较噻二唑与苄基和苯乙烯基相连的结果要好。而2-芳基-喹啉-4-羧酸类化合物的喹啉环与苯环直接相连,4-位羧酸改造可以根据前期噻二唑类HDAC构效关系研究结果可引入长度不同的Linker和锌离子螫合基团(ZBG)。因此我们根据药物设计学中的电子等排原理,应用喹啉环替换原噻二唑HDAC抑制剂的噻二唑环,通过考察Linker和不同形式的ZBG基团,以期研究2-芳基-喹啉-4-甲酰胺类衍生物在抑制HDAC的构效关系。本课题共合成79个2-芳基-喹啉-4-甲酰胺类新化合物,其中目标化合物31个。所有新化合物结构均经过质谱、核磁共振氢谱、碳谱或高分辨质谱确证。目标化合物对HDACs的抑酶活性经过多次活性筛选,最终发现部分目标化合物具有较好的活性,其中目标化合物22d的半数有效浓度(IC50)与阳性对照药SAHA抑酶活性类似。关于该化合物对HDAC亚型选择性和抑制肿瘤细胞增殖的活性实验正在进行中。
综上所述,本论文针对2-芳基-喹啉-4-羧酸衍生物进行一系列深入研究,先后发现该2-芳基硼酸-喹啉-4-羧酸类化合物不仅能够作为识别糖类化合物的荧光探针,而且在与儿茶酚类物质相互作用时的存在荧光淬灭的特殊性质,适于作为识别儿茶酚衍生物的水溶性荧光探针。该探针经结构改造,还发现若干衍生物具有识别多巴胺和左旋多巴等儿茶酚胺类衍生物的功能。另一方面,我们发现2-芳基-喹啉-4-甲酰胺类结构可作为HDACs抑制剂的酶表面识别区域,引入不同的侧链和ZBG基团可具有较强的抑制HDAC活性,是一类新型HDAC抑制剂先导化合物。我们后续工作也将针对本论文的上述研究结果,进行更深入的构效关系研究和生物活性评价。
2-Aryl-quinoline-4-carboxylic acid-based compounds have various biological activities, such as antipyretic analgesic, anti-inflammatory, anti-oxidation, anti-tumor and anti-viral. For example. Cenchophin. was used as the antipyretic analgesic for the treatment of gout. Currently, the application of this agent combining with prednisolone is used to treat arthritis for animal. In the past two decades, a lot of research work have been performed the synthesis and pharmacological studies on2-aryl-quinoline-4-carboxylic acid derivatives. Especially in recent years.2-aryl-quinoline-4-carboxylic acid-based compounds have been reported as chemosensors due to their good fluorescence properties. These compounds could be used for recognize carbohydrates, catecholamines or other life-related substances.
It was reported that2-phenylboronic acid-quinoline-4-carboxylic acid is a new water soluble boronic acid-based fluorescent sensor for carbohydrate. This sensor have the advantages such as significant fluorescence output after binding with carbohydrate and easily optimization for their derivatives.. In our previous studies, a series of diboronic acid based on the fluorescent reporter were synthesized and found one compound could recognize the oligosaccharide. In our recent studies, we found that low concentration of catechol can decrease the fluorescence intensity of this compound, which suggest that2-phenyl-quinoline-4-carboxylic acid could be used as catechol sensor without the interference of the carbohydrate. The detection limit of this compound in rabbit plasma was also resolved as the concentration of catechol, which resulted in a statistically significant decreasing in fluorescence intensity with a p-value<0.01compared with a blank control.
As we knows, catecholamine derivatives, such as dopamine, L-DOPA and adrenaline, are widely existed in human bodies and exhibit various biological effects. Therefore, development of fluorescent sensors for catecholamine derivatives is very important especially for the studies on their monitoring in pathological studies. However,2-phenylboronic acid-quinoline-4-carboxylic acid has no selectivity on catechol and catecholamine derivatives. According to our previous result, the amidation of carboxyl group in this compound didn't influence its binding affinity for catechol derivatives. In addition, the amino group in dopamine and L-DOPA could be used as second binding site for our fluorescent sensor. Therefore, a series of chemosensor were designed and synthesized based on the reporter of catechol and the different linker with carboxylic acid or boronic acid. Totally,47new compounds were synthesized, which include18target compounds identified by MS,'H-NMR,13C-NMR and HRMS. Preliminary studies showed that one compound,9d has stonger binding affinities and selectivies on L-DOPA compared with catechol and dopamine. These results indicated that the length of the linker of target compound has significant influence on the binding affinity and selectivity to L-DOPA. For example, compounds with the linker of one or three methylene units have no selectivity on catechol and catecholamine derivatives. While the linker extend to five methylene unit, the binding affinity and selectivity to L-DOPA could be increased. On the other hand, target compound7h shows the selectivity on dopamine with long emission wavelength for their fluorescence output, which could be helpful to find new long wavelength reporter for dopamine detection.
The second part of this thesis focus on the development of HDAC inhibitors based on2-phenyl-quinoline-4-carboxylic acid. In our previous studies, a series of tetrahydroquinoline and thiadazole derivatives were developed as HDAC inhibitors. As the surface recognition region, thiadazole ring could be replaced by2-phenyl-quinoline according to our previous SAR studies. In our on-going work, different linker and zinc binding group were introduced to the2-phenyl-quinoline-4-carboxylic acid structure, which totally synthezied79new compounds including31new target compounds. All the target compounds were identified by ESI-MS,'H-NMR,13C-NMR or High Resolution Mass Spectrometry. The preliminary binding results showed that, compound5compunds have the IC50value less than1μM and compound22d showed potent HDACs inhibitory similar to SAHA. Further studies on HDACs subtype selectivities and antiproliferative activities are in progress.
In summary, our research work on2-phenyl-quinoline-4-carboxylic acid deriatives showed that these series compounds could used as fluorescent reporter of catechol and HDAC inhibitors after structural modification. The2-phenylboronic acid-quinoline-4-carboxylic acid has the ability of fluorescence quench after addition of catechol derivatives. The structural modification on the4-carboxylic acid could be helpful to find selective fluorescent sensor for L-DOPA and dopamine. On the other hand, different linker and zinc binding group could be introduced to2-phenyl-quinoline-4-carboxamide derivatives, which could be used as lead compound to develop new HDAC inhibitors.
近年来报道的2-芳基硼酸-喹啉-4-羧酸化合物可作为识别糖类物质的水溶性荧光探针。该化合物与糖结合后荧光强度增幅大且结构适于衍生化。本课题组前期曾以该结构为先导,设计、合成一系列二硼酸化合物,并对其针对寡糖的识别作用进行了初步研究。本论文在前期工作的基础上,发现2-芳基硼酸-喹啉-4-羧酸与儿茶酚衍生物相互结合后荧光强度大幅降低。针对这一反常现象,经过多个实验证实引起荧光强度降低的现象是由硼酸化合物引起的,且该硼酸化合物与儿茶酚的亲和力比糖类化合物高。由于该化合物与儿茶酚类物质结合后荧光强度变化与糖类物质趋势正好相反,因此也适于作为选择性识别儿茶酚类物质的荧光探针。我们还应用兔血浆替代缓冲溶液,结果证实荧光强度随儿茶酚浓度升高而显著降低,且浓度依赖性较好,因此该荧光探针可适用于在血浆等生物样本中识别儿茶酚类物质。
儿茶酚物质在体内分布广泛且发挥多种生物活性,特别是儿茶酚胺类物质(如多巴胺,左旋多巴,肾上腺素等)与体内心血管疾病和中枢神经系统疾病有重多关系。研究选择性识别儿茶酚胺类物质的荧光探针具有重要科学和实用意义。然而2-芳基硼酸-喹啉-4-羧酸化合物尽管与儿茶酚亲和力高,但对多巴胺和左旋多巴等儿茶酚胺类物质选择性却不理想。考虑到儿茶酚胺结构中存在游离氨基结构,我们结合过去研究硼酸类荧光探针的经验,在2-芳基硼酸-喹啉-4-羧酸结构中羧酸部位进行改造,引入羧酸或另一个硼酸作为第二识别位点。目标化合物在设计中不仅考虑两个识别位点的性质,还进一步考察不同长度、柔性的连接臂(Linker),以期目标化合物与儿茶酚胺类生命活性物质的亲和力和选择性。在设计、合成的47个新化合物中,目标化合物18个,所有化合物通质谱、核磁共振氢谱、碳谱或高分辨质谱确证。通过初步的荧光活性筛选发现,化合物9d对左旋多巴的亲和力是多巴胺和儿茶酚的两倍,初步实现对左旋多巴的选择性。比较目标化合物9d与其类似物的结构可以发现,喹啉母核结构4-位引入不同链长的烷基羧酸结构对于儿茶酚胺类物质的亲和力有重要影响。当链长为1个或3个碳原子时,新化合物并未显示选择性；当链长为5个碳原子时,化合物9d与左旋多巴的亲和力和选择性均有较大提高,这为今后进一步寻找选择性识别儿茶酚胺物质提供了可供借鉴的新思路。除此之外,活性筛选中还发现目标化合物10h不仅对多巴胺具有较好的选择活性,而且其发射波长(484nm)明显长于先导物2-芳基硼酸-喹啉-4-羧酸(382nm)。这为研究新型长波类水溶性荧光探针提供了新的研究手段和研究工具。
本课题组多年来从事针对组蛋白去乙酰化酶(HDACs)抑制剂的研究,并先后发表了基于四氢异喹啉和噻二唑等杂环的结构类型。根据近期发现的噻二唑类HDAC抑制剂构效关系研究结果,作为HDAC抑制剂表面识别区域的噻二唑与苯环直接相连的化合物活性较噻二唑与苄基和苯乙烯基相连的结果要好。而2-芳基-喹啉-4-羧酸类化合物的喹啉环与苯环直接相连,4-位羧酸改造可以根据前期噻二唑类HDAC构效关系研究结果可引入长度不同的Linker和锌离子螫合基团(ZBG)。因此我们根据药物设计学中的电子等排原理,应用喹啉环替换原噻二唑HDAC抑制剂的噻二唑环,通过考察Linker和不同形式的ZBG基团,以期研究2-芳基-喹啉-4-甲酰胺类衍生物在抑制HDAC的构效关系。本课题共合成79个2-芳基-喹啉-4-甲酰胺类新化合物,其中目标化合物31个。所有新化合物结构均经过质谱、核磁共振氢谱、碳谱或高分辨质谱确证。目标化合物对HDACs的抑酶活性经过多次活性筛选,最终发现部分目标化合物具有较好的活性,其中目标化合物22d的半数有效浓度(IC50)与阳性对照药SAHA抑酶活性类似。关于该化合物对HDAC亚型选择性和抑制肿瘤细胞增殖的活性实验正在进行中。
综上所述,本论文针对2-芳基-喹啉-4-羧酸衍生物进行一系列深入研究,先后发现该2-芳基硼酸-喹啉-4-羧酸类化合物不仅能够作为识别糖类化合物的荧光探针,而且在与儿茶酚类物质相互作用时的存在荧光淬灭的特殊性质,适于作为识别儿茶酚衍生物的水溶性荧光探针。该探针经结构改造,还发现若干衍生物具有识别多巴胺和左旋多巴等儿茶酚胺类衍生物的功能。另一方面,我们发现2-芳基-喹啉-4-甲酰胺类结构可作为HDACs抑制剂的酶表面识别区域,引入不同的侧链和ZBG基团可具有较强的抑制HDAC活性,是一类新型HDAC抑制剂先导化合物。我们后续工作也将针对本论文的上述研究结果,进行更深入的构效关系研究和生物活性评价。
2-Aryl-quinoline-4-carboxylic acid-based compounds have various biological activities, such as antipyretic analgesic, anti-inflammatory, anti-oxidation, anti-tumor and anti-viral. For example. Cenchophin. was used as the antipyretic analgesic for the treatment of gout. Currently, the application of this agent combining with prednisolone is used to treat arthritis for animal. In the past two decades, a lot of research work have been performed the synthesis and pharmacological studies on2-aryl-quinoline-4-carboxylic acid derivatives. Especially in recent years.2-aryl-quinoline-4-carboxylic acid-based compounds have been reported as chemosensors due to their good fluorescence properties. These compounds could be used for recognize carbohydrates, catecholamines or other life-related substances.
It was reported that2-phenylboronic acid-quinoline-4-carboxylic acid is a new water soluble boronic acid-based fluorescent sensor for carbohydrate. This sensor have the advantages such as significant fluorescence output after binding with carbohydrate and easily optimization for their derivatives.. In our previous studies, a series of diboronic acid based on the fluorescent reporter were synthesized and found one compound could recognize the oligosaccharide. In our recent studies, we found that low concentration of catechol can decrease the fluorescence intensity of this compound, which suggest that2-phenyl-quinoline-4-carboxylic acid could be used as catechol sensor without the interference of the carbohydrate. The detection limit of this compound in rabbit plasma was also resolved as the concentration of catechol, which resulted in a statistically significant decreasing in fluorescence intensity with a p-value<0.01compared with a blank control.
As we knows, catecholamine derivatives, such as dopamine, L-DOPA and adrenaline, are widely existed in human bodies and exhibit various biological effects. Therefore, development of fluorescent sensors for catecholamine derivatives is very important especially for the studies on their monitoring in pathological studies. However,2-phenylboronic acid-quinoline-4-carboxylic acid has no selectivity on catechol and catecholamine derivatives. According to our previous result, the amidation of carboxyl group in this compound didn't influence its binding affinity for catechol derivatives. In addition, the amino group in dopamine and L-DOPA could be used as second binding site for our fluorescent sensor. Therefore, a series of chemosensor were designed and synthesized based on the reporter of catechol and the different linker with carboxylic acid or boronic acid. Totally,47new compounds were synthesized, which include18target compounds identified by MS,'H-NMR,13C-NMR and HRMS. Preliminary studies showed that one compound,9d has stonger binding affinities and selectivies on L-DOPA compared with catechol and dopamine. These results indicated that the length of the linker of target compound has significant influence on the binding affinity and selectivity to L-DOPA. For example, compounds with the linker of one or three methylene units have no selectivity on catechol and catecholamine derivatives. While the linker extend to five methylene unit, the binding affinity and selectivity to L-DOPA could be increased. On the other hand, target compound7h shows the selectivity on dopamine with long emission wavelength for their fluorescence output, which could be helpful to find new long wavelength reporter for dopamine detection.
The second part of this thesis focus on the development of HDAC inhibitors based on2-phenyl-quinoline-4-carboxylic acid. In our previous studies, a series of tetrahydroquinoline and thiadazole derivatives were developed as HDAC inhibitors. As the surface recognition region, thiadazole ring could be replaced by2-phenyl-quinoline according to our previous SAR studies. In our on-going work, different linker and zinc binding group were introduced to the2-phenyl-quinoline-4-carboxylic acid structure, which totally synthezied79new compounds including31new target compounds. All the target compounds were identified by ESI-MS,'H-NMR,13C-NMR or High Resolution Mass Spectrometry. The preliminary binding results showed that, compound5compunds have the IC50value less than1μM and compound22d showed potent HDACs inhibitory similar to SAHA. Further studies on HDACs subtype selectivities and antiproliferative activities are in progress.
In summary, our research work on2-phenyl-quinoline-4-carboxylic acid deriatives showed that these series compounds could used as fluorescent reporter of catechol and HDAC inhibitors after structural modification. The2-phenylboronic acid-quinoline-4-carboxylic acid has the ability of fluorescence quench after addition of catechol derivatives. The structural modification on the4-carboxylic acid could be helpful to find selective fluorescent sensor for L-DOPA and dopamine. On the other hand, different linker and zinc binding group could be introduced to2-phenyl-quinoline-4-carboxamide derivatives, which could be used as lead compound to develop new HDAC inhibitors.
引文
1. Cutrin Prieto C. Nieto Pol E. Batalla Eiras A. Casal Iglesias L, Perez Becerra E, Zuniga L. Toxic hepatitis from cinchophen:report of 3 cases. Medicina Clinica.1991; 97(3):104-106.
2. Butters M, Harvey JN. Jover J, Lennox AJ, Lloyd-Jones GC Murray PM. Aryl trifluoroborates in Suzuki-Miyaura coupling:the roles of endogenous aryl boronic acid and fluoride. Angew Chem Int Ed Engl.2010; 49(30):5156-5160.
3. Hogermeier J. Reissig HU. First comprehensive investigation of Suzuki couplings of alkenyl nonaflates with aryl and alkenyl boronic acid derivatives by using classical conditions and microwave heating. Chemistry.2007;13(8):2410-2420.
4. Occhiato EG. Lo Galbo F, Guarna A. Preparation and Suzuki-Miyaura coupling reactions of tetrahydropyridine-2-boronic acid pinacol esters.J Org Chem.2005; 70(18):7324-7330.
5. Ferrier RJ. Carbohydrate Boronates. Adv. Cabohydr. Chem. Biochem.1978;35:31.
6. Sarotti AM, Pisano PL, Pellegrinet SC. A facile microwave-assisted Diels-Alder reaction of vinylboronates. Org Biomol Chem.2010;8(22):5069-5073.
7. Yu H, Wang B. Phenylboronic acids facilitated selective reduction of aldehydes by tributyltin hydride. Synth. Commun.2001;31:163-169.
8. Zheng H, McDonald R. Hall DG. Boronic acid catalysis for mild and selective [3+2] dipolar cycloadditions to unsaturated carboxylic acids. Chemistry.2010;16(18): 5454-5460.
9. Milo LJ, Jr.. Lai JH, Wu W, Liu Y, Maw H. Li Y, Jin Z. Shu Y, Poplawski SE. Wu Y. Sanford DG, Sudmeier JL, Bachovchin WW. Chemical and biological evaluation of dipeptidyl boronic acid proteasome inhibitors for use in prodrugs and pro-soft drugs targeting solid tumors. J Med Chem.2011; 54(13):4365-4377.
10. Albers HM. Hendrickx LJ. van Tol RJ. Hausmann J. Perrakis A. Ovaa H. Structure-based design of novel boronic acid-based inhibitors of autotaxin. J Med Chem.2011;54(13):4619-4626.
11. Poplawski SE, Lai JH, Sanford DG, Sudmeier JL, Wu W, Bachovchin WW. Pro-soft Val-boroPro:a strategy for enhancing in vivo performance of boronic acid inhibitors of serine proteases. J Med Chem.2011; 54(7):2022-2028.
12. Zhu Y,Wu G,Zhu X, Ma Y, Zhao X, Li Y, Yuan Y, Yang J, Yu S, Shao F, Lei M. Synthesis, in vitro and in vivo biological evaluation, and comprehensive understanding of structure-activity relationships of dipeptidyl boronic acid proteasome inhibitors constructed from beta-amino acids. J Med Chem.2010;55(24): 8619-8626.
13. Ke W, Sampson JM, Ori C, Prati F, Drawz SM, Bethel CR, Bonomo RA, van den Akker F. Novel insights into the mode of inhibition of class A SHV-1 beta-lactamases revealed by boronic acid transition state inhibitors. Antimicrob Agents Chemother. 2011:55(1):174-183.
14. Watanabe T, Abe H, Momose I, Takahashi Y, Ikeda D, Akamatsu Y. Structure-activity relationship of boronic acid derivatives of tyropeptin:proteasome inhibitors. Bioorg Med Chem Lett.2010;20(19):5839-5842.
15. Albers HM, van Meeteren LA, Egan DA, van Tilburg EW, Moolenaar WH,Ovaa H.Discovery and optimization of boronic acid based inhibitors of autotaxin.J Med Chem.2010;55(13):4958-4967.
16. Tondi D, Calo S, Shoichet BK, Costi MP. Structural study of phenyl boronic acid derivatives as AmpC beta-lactamase inhibitors.Bioorg Med Chem Lett.2010;20(11): 3416-3419.
17. Zhu Y, Zhu X, Wu G, Ma Y, Li Y, Zhao X, Yuan Y, Yang J, Yu S, Shao F, Li R, Ke Y. Lu A, Liu Z, Zhang L. Synthesis, in vitro and in vivo biological evaluation, docking studies, and structure--activity relationship (SAR) discussion of dipeptidyl boronic acid proteasome inhibitors composed of beta-amino acids. J Med Chem.2010; 55(5):1990-1999.
18. LORAND JP, EDWARDS JO.Polyol complexes and structure of the benzeneboronate ion. The Journal of Organic Chemistry.1959;24(6):769-774.
19. Yoon J, Czarnik AW. Fluorescent chemosensors of carbohydrates. A means of chemically communicating the binding of polyols in water based on chelation-enhanced quenching. Journal of the American Chemical Society.1992; 114(14):5874-5875.
20. Springsteen G, Wang B. A detailed examination of boronic acid-diol complexation. Tetrahedron.2002;55(26):5291-5300.
21.James T, Shinkai S. Artificial receptors as chemosensors for carbohydrates. Host-Guest Chemistry.2002:159-200.
22. Yang W. Yan J, Springsteen G, Deeter S. Wang B. A novel type of fluorescent boronic acid that shows large fluorescence intensity changes upon binding with a carbohydrate in aqueous solution at physiological pH. Bioorganic & medicinal chemistry letters.2003;75(6):1019-1022.
23. Yang W. Lin L, Wang B. A new type of boronic acid fluorescent reporter compound for sugar recognition. Tetrahedron letters.2005;46(46):7981-7984.
24. James TD. Sandanayake KRAS. Shinkai S. Novel photoinduced electron-transfer sensor for saccharides based on the interaction of boronic acid and amine. Journal of the Chemical Society Chemical Communications.1994(4):477-478.
25. James TD, Sandanayake KRAS, Iguchi R, Shinkai S. Novel saccharide-photoinduced electron transfer sensors based on the interaction of boronic acid and amine. Journal of the American Chemical Society.1995;777(35): 8982-8987.
26. Du L,Li M,Zheng S, Wang B. Rational Design of a Fluorescent Hydrogen Peroxide Probe Based on the Umbelliferone Fluorophore. Tetrahedron Lett.2008; 79(19):3045-3048.
27. Coskun A. Akkaya EU. Three-point recognition and selective fluorescence sensing of L-DOPA. Org Lett.2004;6(18):3107-3109.
28. Yang W, Lin L. Wang B. A new type of water-soluble fluorescent boronic acid suitable for construction of polyboronic acids for carbohydrate recognition. Heterocyclic Communications.2011;10(6):383-388.
29. Perini R. Fiorucci S. Wallace JL. Mechanisms of nonsteroidal anti-inflammatory drug-induced gastrointestinal injury and repair:a window of opportunity for cyclooxygenase-inhibiting nitric oxide donors. Can J G astro enterol.2004;18(4): 229-236.
30. Radi ZA, Khan NK. Effects of cyclooxygenase inhibition on the gastrointestinal tract. Exp Toxicol Pathol.2006;55(2-3):163-173.
31. Meyer-Kirchrath J, Schror K. Cyclooxygenase-2 inhibition and side-effects of non-steroidal anti-inflammatory drugs in the gastrointestinal tract. Curr Med Chem. 2000;7(11):1121-1129.
32. Vane J, Botting R. Anti-inflammatory drugs and their mechanism of action. Inflammation Research.1998;47(14):78-87.
33. Cummings JL. Depression and Parkinson's disease:A review. The American journal of psychiatry.1992.
34. Tsuboi Y. Environmental-genetic interactions in the pathogenesis of Parkinson's disease. Exp Newobiol.2012;21(3):123-128.
35. Ghodsi R. Zarghi A. Daraei B. Hedayati M. Design, synthesis and biological evaluation of new 2,3-diarylquinoline derivatives as selective cyclooxygenase-2 inhibitors. Bioorg Med Chem.2010;75(3):1029-1033.
36. Zarghi A, Ghodsi R. Azizi E, Daraie B, Hedayati M, Dadrass OG. Synthesis and biological evaluation of new 4-carboxyl quinoline derivatives as cyclooxygenase-2 inhibitors. Bioorg Med Chem.2009;17(14):5312-5317.
37. Ryan US. Worthington RE. Cell-cell contact mechanisms. Curr Opin Immunol. 1992;4(1):33-37.
38. Kaila N, Janz K, DeBernardo S, Bedard PW, Camphausen RT, Tam S, Tsao DHH, Keith Jr JC. Nickerson-Nutter C, Shilling A. Synthesis and biological evaluation of quinoline salicylic acids as P-selectin antagonists. Journal of medicinal chemistry. 2007;50(1):21-39.
39. Bedard PW. Clerin V, Sushkova N, Tchernychev B, Antrilli T. Resmini C, Keith JC, Jr., Hennan JK, Kaila N, Debernardo S, Janz K. Wang Q, Crandall DL, Schaub RG, Shaw GD,Carter LL.Characterization of the novel P-selectin inhibitor PSI-697 [2-(4-chlorobenzyl)-3-hydroxy-7.8,9.10-tetrahydrobenzo[h] quinoline-4-carboxylic acid] in vitro and in rodent models of vascular inflammation and thrombosis. J Pharmacol Exp Ther.2008; 324(2):497-506.
40. Kaila N. Janz K, Huang A. Moretto A, DeBernardo S,Bedard PW, Tam S, Clerin V, Keith JC, Jr., Tsao DH, Sushkova N, Shaw GD, Camphausen RT, Schaub RG, Wang Q.2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H] quinoline-4-carboxylic acid (PSI-697):identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists. J Med Chem.2007; 50(1):40-64.
41. Myers DD, Jr., Rectenwald JE, Bedard PW, Kaila N, Shaw GD, Schaub RG Farris DM, Hawley AE, Wrobleski SK, Henke PK, Wakefield TW. Decreased venous thrombosis with an oral inhibitor of P selectin. J Vase Surg.2005;42(2):329-336.
42. Myers Jr DD, Wrobleski SK, Longo C, Bedard PW, Kaila N. Shaw GD,Londy FJ, Rohrer SE. Fex BA, Zajkowski PJ. Resolution of venous thrombosis using a novel oral small-molecule inhibitor of P-selectin (PSI-697) without anticoagulation. Thrombosis and haemostasis.2007;97(3):400.
43. Natale R. Wheeler R. Moore M,Dallaire B,Lynch W, Carlson R, Grillo-Lopez A, Gyves J. Multicenter phase Ⅱ trial of brequinar sodium in patients with advanced melanoma.Ann Oncol.1992;5(8):659-660.
44. Cody R, Stewart D, DeForni M, Moore M, Dallaire B. Azamia N, Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced breast cancer. Am J Clin Oncol 1993;16(6):526-528.
45. Maroun J, Ruckdeschel J, Natale R. Morgan R, Dallaire B, Sisk R. Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced lung cancer. Cancer Chemother Pharmacol.1993;32(1):64-66.
46. Moore M, Maroun J, Robert F, Natale R, Neidhart J, Dallaire B, Sisk R, Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced gastrointestinal cancer. Invest New Drugs.1993;77(1):61-65.
47. Joshi AS, King SY. Zajac BA, Makowka L, Sher LS, Kahan BD,Menkis AH, Stiller CR. Schaefle B, Kornhauser DM. Phase I safety and pharmacokinetic studies of brequinar sodium after single ascending oral doses in stable renal, hepatic, and cardiac allograft recipients. JClin Pharmacol 1997:57(12):1121-1128.
48. Qing M, Zou G, Wang QY, Xu HY. Dong H. Yuan Z, Shi PY. Characterization of dengue virus resistance to brequinar in cell culture. Antimicrobial agents and chemotherapy.2010;54(9):3686-3695.
1. Suk KT, Kim HS, Kim MY, Kim JW, Uh Y, Jang IH, Kim SK, Choi EH. Kim MJ, Joo.IS, Baik SK. In vitro antibacterial and morphological effects of the urushiol component of the sap of the Korean lacquer tree (Rhus vernicifera Stokes) on Helicobacter pylori. J Korean Med Sci.2010;25(3):399-404.
2. Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology.2006;6(5(1):17-22.
3. Beck G, Brinkkoetter P, Hanusch C, Schulte J, van Ackem K, van der Woude FJ, Yard BA. Clinical review:immunomodulatory effects of dopamine in general inflammation.Cril Care.2004;8(6):485-491.
4.Rye DB. The two faces of Eve:dopamine's modulation of wakefulness and sleep. Neurology.2004;63(8 Suppl 3):S2-7.
5. Weissmann G, Vosshall LB. Bayer CA. Dunham PB. Marine sponge aggregation:a model for effects of NSAIDs on the calcium movements of cell activation. Semin Arthritis Rheum.1985;15(2 Suppl 1):42-53.
6. Dunham PB. Vosshall LB, Bayer CA, Rich AM, Weissmann G. From Beaumont to poison ivy:marine sponge cell aggregation and the secretory basis of inflammation. Fed Proc.1985;44(14):2914-2924.
7. Allen PL. Leaves of three, let them be:if it were only that easy! Pediatr Nurs.2004; 30(2):129-135.
8. Zhang M. Gong K, Zhang H, Mao L. Layer-by-layer assembled carbon nanotubes for selective determination of dopamine in the presence of ascorbic acid. Biosensors and Bioelectronics.2005; 20(1):1270-1276.
9. Yi W. Liang W, Li Y, Li P, Zhang Z. Chen A, Hu C. Electrocatalytic Oxidation and Determination of Dopamine Concentrations Based on Fe3O4-Polyaniline Nanoparticles/Glutamic Acid Chemically Modified Electrodes. Sensor Letters.2010; 8(6):760-766.
10. Tsunoda M, Aoyama C, Nomura H. Toyoda T. Matsuki N. Funatsu T. Simultaneous determination of dopamine and 3.4-dihydroxyphenylacetic acid in mouse striatum using mixed-mode reversed-phase and cation-exchange high-performance liquid chromatography. Journal of pharmaceutical and biomedical analysis.2010;57(3):712-715.
11. Tang H, Lin P, Chan HLW, Yan F. Highly sensitive dopamine biosensors based on organic electrochemical transistors. Biosensors and Bioelectronics.2011;26(11): 4559-4563.
12. Secor KE, Timothy E. Selective amine recognition:development of a chemosensor for dopamine and norepinephrine. Organic letters.2004;6(21): 3727-3730.
13.Raoof JB, Kiani A, Ojani R, Valiollahi R. Electrochemical Determination-of Dopamine Using Banana-MWCNTs Modified Carbon Paste Electrode.2011.26(11): 4559-4563.
14. Pietrzyk A,Suriyanarayanan S, Kutner W, Maligaspe E, Zandler ME. D'Souza F. Molecularly imprinted poly [bis (2,2'-bithienyl) methane] film with built-in molecular recognition sites for a piezoelectric microgravimetry chemosensor for selective determination of dopamine. Bioelectrochemistry.2010.26(21):459-463.
15. Mahshid S, Li C, Mahshid SS, Askari M, Dolati A, Yang L. Luo S, Cai Q. Sensitive determination of dopamine in the presence of uric acid and ascorbic acid using TiO2 nanotubes modified with Pd. Pt and Au nanoparticles. Analyst.2011. 26(11):4559-4963.
16. Lin X, Zhang Y, Chen W. Wu P. Electrocatalytic oxidation and determination of dopamine in the presence of ascorbic acid and uric acid at a poly (p-nitrobenzenazo resorcinol) modified glassy carbon electrode. Sensors and Actuators B:Chemical. 2007; 122(1):309-314.
17. Li CY, Cai YJ, Yang CH. Wu CH, Wei Y, Wen TC, Wang TL. Shieh YT, Lin WC, Chen WJ. Highly sensitive and selective electrochemical determination of dopamine and ascorbic acid at Ag/Ag2S modified electrode. Electrochimica Acta.2010;56(5): 1955-1959.
18. Fengyun H, Minsheng L, Zifeng Z, Fengzhu Y, Guangyuan S. Electrochemical Behavior and Determination of Dopamine at ZnO Nanorods Intercalated Graphite Modified Electrode [J]. Chinese Journal of Applied Chemistry.2011; 25(03): 320-325.
19. Farzin L, Hosseini MRM. Simultaneous Determination of Dopamine and L-Ascorbic Acid by Modified Carbon Paste Electrode with Ni (Ⅱ) Cyclam Complex. American Journal of Analytical Chemistry.2011:2.26-99
20. Erickson CK. Review of neurotransmitters and their role in alcoholism treatment. Alcohol and Alcoholism.1996;31(suppl):5.
21. Chandra U, Swamy BEK, Gilbert O, Reddy S, Sherigara B. Determination of Dopamine in Presence of Uric Acid at Poly (Eriochrome Black t) Film Modified Graphite Pencil Electrode. American Journal of Analytical Chemistry. 2011:2:78-90
22. Atta NF, Galal A. Abu-Attia FM, Azab SM. Carbon Paste Gold Nanoparticles Sensor for the Selective Determination of Dopamine in Buffered Solutions. Journal of The Electrochemical Society.2010;157:F116-F123.
23. Abbaspour A, Valizadeh H. Khajehzadeh A. A simple, fast and cost effective method for detection and determination of dopamine in bovine serum. Anal. Methods. 2011;3(6):1405-1409.
24. Gorina AS. KolesnichenkoLS, Mikhnovich Ⅵ. Catecholamines and their metabolites in children with Asperger and Kanner syndromes. Biomed Khim.2011; 57(5):562-570.
25. Hamdy NM, El-Wakeel L, Suwailem SM. Involvement of Depressive Catecholamines as Thrombosis Risk/Inflammatory Markers in Non-Smoker, Non-Obese Congestive Heart Failure. Linked to Increased Epidermal Growth Factor-Receptor (EGF-R) Production. Indian J Clin Biochem.2011;26(2):140-145.
26. Riva R. Mork PJ. Westgaard RH, Okkenhaug Johansen T, Lundberg U Catecholamines and heart rate in female fibromyalgia patients.J Psychosom Res. 2012;72(1):51-57.
27. Vuda M, Brander L, Schroder R, Jakob SM, Takala J, Djafarzadeh S. Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs. Innate Immun.2012;18(2):217-230.
28. Peterson G. Kumar A,Gart E, Narayanan S.Catecholamines increase conjugative gene transfer between enteric bacteria. Microb Paihog.2011;57(1-2):1-8.
29. Kotecha R,Toledo-Pereyra LH. The effect of catecholamines on hepatic artery vasospasm in small-for-size syndrome liver grafts. J Surg Res.2012:172(1):77-79.
30. Holloway EL, Polumbo RA, Harrison DC. Acute circulatory effects of dopamine in patients with pulmonary hypertension. British heart journal.1975;37(5):482-485.
31. Lv H, Li A, Liu F. Ma H, Yao B. Effects of gastrodin on the dopamine system of Tourette's syndrome rat models. Biosci Trends.2009;5(2):58-62.
32. Cotzias GC, Papavasiliou PS.Gellene R. Modification of Parkinsonism—chronic treatment with L-dopa. New England Journal of Medicine.1969;280(1):337-345.
33. Paisan-Ruiz C, Guevara R. Federoff M.Hanagasi H, Sina F. Elahi E, Schneider SA. Schwingenschuh P. Bajaj N, Emre M. Early- onset L -dopa- responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6. FBXO7 and spatacsin mutations. Movement Disorders.2010;25(12):1791-1800.
34. Sagar KA. Smyth MR. Simultaneous determination of levodopa, carbidopa and their metabolites in human plasma and urine samples using LC-EC. J Pharm Biomed Anal.2000;22:613-624.
35. Karimi M. Carl JL. Loftin S. Perlmutter JS. Modified high-performance liquid chromatography with electrochemical detection method for plasma measurement of levodopa,3-O-methyldopa, dopamine, carbidopa and 3,4-dihydroxyphenyl acetic acid. J Chromatogr B Analyt Technol Biomed Life Sci.2006;836:120-123.
36. Talebpour Z, Haghgoo S, Shamsipur M.1H nuclear magnetic resonance spectroscopy analysis for simultaneous determination of levodopa. carbidopa and methyldopa in human serum and pharmaceutical formulations. Analytica Chimica Acta.2004;506:97-104.
37. Ha PT, Van Schepdael A. Hauta-Aho T, Roets E. Hoogmartens J. Simultaneous detennination of dopa and carbidopa enantiomers by capillary zone electrophoresis. Electrophoresis.2002;25(19):3404-3409.
38. Seto D. Maki T, Soh N, Nakano K. Ishimatsu R, Imato T. A simple and selective fluorometric assay for dopamine using a calcein blue-Fe2+ complex fluorophore. Talanta.2012:94:36-43.
39. Coskun A. Akkaya EU. Three-point recognition and selective fluorescence sensing of L-DOPA. Org Lett.2004;6(18):3107-3109.
40. Wu Z, Zhao H, Xue Y, He Y, Li X, Yuan Z. Colorimetric determination of melamine by pyridine-3-boronic acid modified gold nanoparticles. J Nanosci Nanotechnol 2012;12(3):2412-2416.
41.Lindwall H, Bandes J, Weinberg I. Preparation of certain brominated cinchophens. Journal of the American Chemical Society.1931;53(1):317-319.
1. Zhang L, Fang H, Xu W. Strategies in developing promising histone deacetylase inhibitors. Medicinal Research Reviews.2010;30(4):585-602.
2. Mai A, Massa S. Rotili D, Cerbara I, Valente S, Pezzi R, Simeoni S, Ragno R. Histone deacetylation in epigenetics:an attractive target for anticancer therapy. Medicinal Research Reviews.2005;25(3):261-309.
3. Itoh Y, Suzuki T, Miyata N. Isoform-selective histone deacetylase inhibitors. Curr Pharm Des.2008;14(6):529-544.
4. Carew JS, Giles FJ, Nawrocki ST. Histone deacetylase inhibitors:mechanisms of cell death and promise in combination cancer therapy. Cancer Letters.2008;269(1): 7-17.
5. Mielcarek M, Benn CL. Franklin SA. Smith DL, Woodman B, Marks PA, Bates GP. SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's disease. PLoS One.2011; 6(11): e27746.
6. Singh J, Khan M. Singh I. HDAC inhibitor SAHA normalizes the levels of VLCFAs in human skin fibroblasts from X-ALD patients and downregulates the expression of proinflammatory cytokines in Abcd1/2-silenced mouse astrocytes. Journal Of Lipid Research.2011; 52(11):2056-2069.
7. Wang L, Zou X, Berger AD, Twiss C, Peng Y, Li Y, Chiu J, Guo H, Satagopan J, Wilton A, Gerald W, Basch R, Wang Z, Osman I, Lee P. Increased expression of histone deacetylaces (HDACs) and inhibition of prostate cancer growth and invasion by HDAC inhibitor SAHA. Am J Transl Res.2009;7(1):62-71.
8. Bieliauskas AV, Weerasinghe SV, Pflum MK. Structural requirements of HDAC inhibitors:SAHA analogs functionalized adjacent to the hydroxamic acid. Bioorganic & Medicinal Chemistry Letters.2007;77(8):2216-2219.
9. Guan P, Fang H. Clinical development of histone deacetylase inhibitor romidepsin. Drug Discov Ther.2010;4(6):388-391.
10. Fiser. A.:Sali, A., Modeller: generation and refinement of homology-based protein structure models.Methods Enzymol 2003:374.461-91.
11. Wang, D. F.;Helquist, P.;Wiech, N.L.;Wiest, O.,Toward selective histone deacetylase inhibitor design:homology modeling, docking studies, and molecular dynamics simulations of human class I histone deacetylases. J Med Chem 2005; 48 (22).6936-47.
12. Morris, G. M.; Huey. R.; Lindstrom, W.; Sanner. M. F.; Belew. R. K.; Goodsell, D. S.; Olson. A. J.,AutoDock4 and AutoDockTools4:Automated docking with selective receptor flexibility. J Comput Chem 2009;30(16),2785-91.
13. Stewart, J. J., MOPAC:a semiempirical molecular orbital program. J Comput Aided Mol Des 1990,4(1),1-105.
14. Jakalian, A.; Jack, D. B.; Bayly, C. I., Fast, efficient generation of high-quality atomic charges. AM1-BCC model:Ⅱ. Parameterization and validation. J Comput Chem 2002,23(16),1623-41.
15. Moore M. Maroun J, Robert F, Natale R, Neidhart J, Dallaire B. Sisk R, Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced gastrointestinal cancer. Invest New Drugs.1993; 77(1):61-65.
16. Maroun J, Ruckdeschel J, Natale R, Morgan R, Dallaire B, Sisk R, Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced lung cancer. Cancer Chemother Pharmacol.1993;32(1):64-66.
17. Qing M, Zou G, Wang QY, Xu HY, Dong H, Yuan Z, Shi PY. Characterization of dengue virus resistance to brequinar in cell culture. Antimicrobial agents and chemotherapy.2010;54(9):3686-3695.
1. Flagstad φ, Andersen R, Wardig C, Johansson M, Breseth H, Ellegren H. Populasjonsovervaking av jerv i Skandinavia ved hjelp av DNA-analyse fra ekskrementer. NINA Rapport 165:42 pp.2006; 165.
2. Angibaud P. Van Emelen K. Arts J. Histone Deacetylase Inhibitors:A Brief Overview Of Their Role And Medicinal Chemistry. Burger's Medicinal Chemistry, Drug Discovery and Development.2010.
3. Boumber Y. Younes A. Garcia-Manero G. Mocetinostat (MGCD0103):a review of an isotype-specific histone deacetylase inhibitor. Expert opinion on investigationl drugs.2011:20(6):823-829.
4. Khaskhely N, Buglio D, Shafer J, Bollard C, Younes A. The histone deacetylase (HDAC) inhibitor entinostat (SNDX-275) targets Hodgkin lymphoma through a dual mechanism of immune modulation and apoptosis induction. Blood (ASH Annual Meeting Abstracts).2009;114:1562.
5. Piekarz RL, Frye R, Turner M. Wright JJ, Allen SL, Kirschbaum MH,Zain J, Prince HM. Leonard JP. Geskin LJ. Phase Ⅱ multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma.Journal of clinical oncology.2009:27(32):5410-5417.
2. Butters M, Harvey JN. Jover J, Lennox AJ, Lloyd-Jones GC Murray PM. Aryl trifluoroborates in Suzuki-Miyaura coupling:the roles of endogenous aryl boronic acid and fluoride. Angew Chem Int Ed Engl.2010; 49(30):5156-5160.
3. Hogermeier J. Reissig HU. First comprehensive investigation of Suzuki couplings of alkenyl nonaflates with aryl and alkenyl boronic acid derivatives by using classical conditions and microwave heating. Chemistry.2007;13(8):2410-2420.
4. Occhiato EG. Lo Galbo F, Guarna A. Preparation and Suzuki-Miyaura coupling reactions of tetrahydropyridine-2-boronic acid pinacol esters.J Org Chem.2005; 70(18):7324-7330.
5. Ferrier RJ. Carbohydrate Boronates. Adv. Cabohydr. Chem. Biochem.1978;35:31.
6. Sarotti AM, Pisano PL, Pellegrinet SC. A facile microwave-assisted Diels-Alder reaction of vinylboronates. Org Biomol Chem.2010;8(22):5069-5073.
7. Yu H, Wang B. Phenylboronic acids facilitated selective reduction of aldehydes by tributyltin hydride. Synth. Commun.2001;31:163-169.
8. Zheng H, McDonald R. Hall DG. Boronic acid catalysis for mild and selective [3+2] dipolar cycloadditions to unsaturated carboxylic acids. Chemistry.2010;16(18): 5454-5460.
9. Milo LJ, Jr.. Lai JH, Wu W, Liu Y, Maw H. Li Y, Jin Z. Shu Y, Poplawski SE. Wu Y. Sanford DG, Sudmeier JL, Bachovchin WW. Chemical and biological evaluation of dipeptidyl boronic acid proteasome inhibitors for use in prodrugs and pro-soft drugs targeting solid tumors. J Med Chem.2011; 54(13):4365-4377.
10. Albers HM. Hendrickx LJ. van Tol RJ. Hausmann J. Perrakis A. Ovaa H. Structure-based design of novel boronic acid-based inhibitors of autotaxin. J Med Chem.2011;54(13):4619-4626.
11. Poplawski SE, Lai JH, Sanford DG, Sudmeier JL, Wu W, Bachovchin WW. Pro-soft Val-boroPro:a strategy for enhancing in vivo performance of boronic acid inhibitors of serine proteases. J Med Chem.2011; 54(7):2022-2028.
12. Zhu Y,Wu G,Zhu X, Ma Y, Zhao X, Li Y, Yuan Y, Yang J, Yu S, Shao F, Lei M. Synthesis, in vitro and in vivo biological evaluation, and comprehensive understanding of structure-activity relationships of dipeptidyl boronic acid proteasome inhibitors constructed from beta-amino acids. J Med Chem.2010;55(24): 8619-8626.
13. Ke W, Sampson JM, Ori C, Prati F, Drawz SM, Bethel CR, Bonomo RA, van den Akker F. Novel insights into the mode of inhibition of class A SHV-1 beta-lactamases revealed by boronic acid transition state inhibitors. Antimicrob Agents Chemother. 2011:55(1):174-183.
14. Watanabe T, Abe H, Momose I, Takahashi Y, Ikeda D, Akamatsu Y. Structure-activity relationship of boronic acid derivatives of tyropeptin:proteasome inhibitors. Bioorg Med Chem Lett.2010;20(19):5839-5842.
15. Albers HM, van Meeteren LA, Egan DA, van Tilburg EW, Moolenaar WH,Ovaa H.Discovery and optimization of boronic acid based inhibitors of autotaxin.J Med Chem.2010;55(13):4958-4967.
16. Tondi D, Calo S, Shoichet BK, Costi MP. Structural study of phenyl boronic acid derivatives as AmpC beta-lactamase inhibitors.Bioorg Med Chem Lett.2010;20(11): 3416-3419.
17. Zhu Y, Zhu X, Wu G, Ma Y, Li Y, Zhao X, Yuan Y, Yang J, Yu S, Shao F, Li R, Ke Y. Lu A, Liu Z, Zhang L. Synthesis, in vitro and in vivo biological evaluation, docking studies, and structure--activity relationship (SAR) discussion of dipeptidyl boronic acid proteasome inhibitors composed of beta-amino acids. J Med Chem.2010; 55(5):1990-1999.
18. LORAND JP, EDWARDS JO.Polyol complexes and structure of the benzeneboronate ion. The Journal of Organic Chemistry.1959;24(6):769-774.
19. Yoon J, Czarnik AW. Fluorescent chemosensors of carbohydrates. A means of chemically communicating the binding of polyols in water based on chelation-enhanced quenching. Journal of the American Chemical Society.1992; 114(14):5874-5875.
20. Springsteen G, Wang B. A detailed examination of boronic acid-diol complexation. Tetrahedron.2002;55(26):5291-5300.
21.James T, Shinkai S. Artificial receptors as chemosensors for carbohydrates. Host-Guest Chemistry.2002:159-200.
22. Yang W. Yan J, Springsteen G, Deeter S. Wang B. A novel type of fluorescent boronic acid that shows large fluorescence intensity changes upon binding with a carbohydrate in aqueous solution at physiological pH. Bioorganic & medicinal chemistry letters.2003;75(6):1019-1022.
23. Yang W. Lin L, Wang B. A new type of boronic acid fluorescent reporter compound for sugar recognition. Tetrahedron letters.2005;46(46):7981-7984.
24. James TD. Sandanayake KRAS. Shinkai S. Novel photoinduced electron-transfer sensor for saccharides based on the interaction of boronic acid and amine. Journal of the Chemical Society Chemical Communications.1994(4):477-478.
25. James TD, Sandanayake KRAS, Iguchi R, Shinkai S. Novel saccharide-photoinduced electron transfer sensors based on the interaction of boronic acid and amine. Journal of the American Chemical Society.1995;777(35): 8982-8987.
26. Du L,Li M,Zheng S, Wang B. Rational Design of a Fluorescent Hydrogen Peroxide Probe Based on the Umbelliferone Fluorophore. Tetrahedron Lett.2008; 79(19):3045-3048.
27. Coskun A. Akkaya EU. Three-point recognition and selective fluorescence sensing of L-DOPA. Org Lett.2004;6(18):3107-3109.
28. Yang W, Lin L. Wang B. A new type of water-soluble fluorescent boronic acid suitable for construction of polyboronic acids for carbohydrate recognition. Heterocyclic Communications.2011;10(6):383-388.
29. Perini R. Fiorucci S. Wallace JL. Mechanisms of nonsteroidal anti-inflammatory drug-induced gastrointestinal injury and repair:a window of opportunity for cyclooxygenase-inhibiting nitric oxide donors. Can J G astro enterol.2004;18(4): 229-236.
30. Radi ZA, Khan NK. Effects of cyclooxygenase inhibition on the gastrointestinal tract. Exp Toxicol Pathol.2006;55(2-3):163-173.
31. Meyer-Kirchrath J, Schror K. Cyclooxygenase-2 inhibition and side-effects of non-steroidal anti-inflammatory drugs in the gastrointestinal tract. Curr Med Chem. 2000;7(11):1121-1129.
32. Vane J, Botting R. Anti-inflammatory drugs and their mechanism of action. Inflammation Research.1998;47(14):78-87.
33. Cummings JL. Depression and Parkinson's disease:A review. The American journal of psychiatry.1992.
34. Tsuboi Y. Environmental-genetic interactions in the pathogenesis of Parkinson's disease. Exp Newobiol.2012;21(3):123-128.
35. Ghodsi R. Zarghi A. Daraei B. Hedayati M. Design, synthesis and biological evaluation of new 2,3-diarylquinoline derivatives as selective cyclooxygenase-2 inhibitors. Bioorg Med Chem.2010;75(3):1029-1033.
36. Zarghi A, Ghodsi R. Azizi E, Daraie B, Hedayati M, Dadrass OG. Synthesis and biological evaluation of new 4-carboxyl quinoline derivatives as cyclooxygenase-2 inhibitors. Bioorg Med Chem.2009;17(14):5312-5317.
37. Ryan US. Worthington RE. Cell-cell contact mechanisms. Curr Opin Immunol. 1992;4(1):33-37.
38. Kaila N, Janz K, DeBernardo S, Bedard PW, Camphausen RT, Tam S, Tsao DHH, Keith Jr JC. Nickerson-Nutter C, Shilling A. Synthesis and biological evaluation of quinoline salicylic acids as P-selectin antagonists. Journal of medicinal chemistry. 2007;50(1):21-39.
39. Bedard PW. Clerin V, Sushkova N, Tchernychev B, Antrilli T. Resmini C, Keith JC, Jr., Hennan JK, Kaila N, Debernardo S, Janz K. Wang Q, Crandall DL, Schaub RG, Shaw GD,Carter LL.Characterization of the novel P-selectin inhibitor PSI-697 [2-(4-chlorobenzyl)-3-hydroxy-7.8,9.10-tetrahydrobenzo[h] quinoline-4-carboxylic acid] in vitro and in rodent models of vascular inflammation and thrombosis. J Pharmacol Exp Ther.2008; 324(2):497-506.
40. Kaila N. Janz K, Huang A. Moretto A, DeBernardo S,Bedard PW, Tam S, Clerin V, Keith JC, Jr., Tsao DH, Sushkova N, Shaw GD, Camphausen RT, Schaub RG, Wang Q.2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H] quinoline-4-carboxylic acid (PSI-697):identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists. J Med Chem.2007; 50(1):40-64.
41. Myers DD, Jr., Rectenwald JE, Bedard PW, Kaila N, Shaw GD, Schaub RG Farris DM, Hawley AE, Wrobleski SK, Henke PK, Wakefield TW. Decreased venous thrombosis with an oral inhibitor of P selectin. J Vase Surg.2005;42(2):329-336.
42. Myers Jr DD, Wrobleski SK, Longo C, Bedard PW, Kaila N. Shaw GD,Londy FJ, Rohrer SE. Fex BA, Zajkowski PJ. Resolution of venous thrombosis using a novel oral small-molecule inhibitor of P-selectin (PSI-697) without anticoagulation. Thrombosis and haemostasis.2007;97(3):400.
43. Natale R. Wheeler R. Moore M,Dallaire B,Lynch W, Carlson R, Grillo-Lopez A, Gyves J. Multicenter phase Ⅱ trial of brequinar sodium in patients with advanced melanoma.Ann Oncol.1992;5(8):659-660.
44. Cody R, Stewart D, DeForni M, Moore M, Dallaire B. Azamia N, Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced breast cancer. Am J Clin Oncol 1993;16(6):526-528.
45. Maroun J, Ruckdeschel J, Natale R. Morgan R, Dallaire B, Sisk R. Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced lung cancer. Cancer Chemother Pharmacol.1993;32(1):64-66.
46. Moore M, Maroun J, Robert F, Natale R, Neidhart J, Dallaire B, Sisk R, Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced gastrointestinal cancer. Invest New Drugs.1993;77(1):61-65.
47. Joshi AS, King SY. Zajac BA, Makowka L, Sher LS, Kahan BD,Menkis AH, Stiller CR. Schaefle B, Kornhauser DM. Phase I safety and pharmacokinetic studies of brequinar sodium after single ascending oral doses in stable renal, hepatic, and cardiac allograft recipients. JClin Pharmacol 1997:57(12):1121-1128.
48. Qing M, Zou G, Wang QY, Xu HY. Dong H. Yuan Z, Shi PY. Characterization of dengue virus resistance to brequinar in cell culture. Antimicrobial agents and chemotherapy.2010;54(9):3686-3695.
1. Suk KT, Kim HS, Kim MY, Kim JW, Uh Y, Jang IH, Kim SK, Choi EH. Kim MJ, Joo.IS, Baik SK. In vitro antibacterial and morphological effects of the urushiol component of the sap of the Korean lacquer tree (Rhus vernicifera Stokes) on Helicobacter pylori. J Korean Med Sci.2010;25(3):399-404.
2. Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology.2006;6(5(1):17-22.
3. Beck G, Brinkkoetter P, Hanusch C, Schulte J, van Ackem K, van der Woude FJ, Yard BA. Clinical review:immunomodulatory effects of dopamine in general inflammation.Cril Care.2004;8(6):485-491.
4.Rye DB. The two faces of Eve:dopamine's modulation of wakefulness and sleep. Neurology.2004;63(8 Suppl 3):S2-7.
5. Weissmann G, Vosshall LB. Bayer CA. Dunham PB. Marine sponge aggregation:a model for effects of NSAIDs on the calcium movements of cell activation. Semin Arthritis Rheum.1985;15(2 Suppl 1):42-53.
6. Dunham PB. Vosshall LB, Bayer CA, Rich AM, Weissmann G. From Beaumont to poison ivy:marine sponge cell aggregation and the secretory basis of inflammation. Fed Proc.1985;44(14):2914-2924.
7. Allen PL. Leaves of three, let them be:if it were only that easy! Pediatr Nurs.2004; 30(2):129-135.
8. Zhang M. Gong K, Zhang H, Mao L. Layer-by-layer assembled carbon nanotubes for selective determination of dopamine in the presence of ascorbic acid. Biosensors and Bioelectronics.2005; 20(1):1270-1276.
9. Yi W. Liang W, Li Y, Li P, Zhang Z. Chen A, Hu C. Electrocatalytic Oxidation and Determination of Dopamine Concentrations Based on Fe3O4-Polyaniline Nanoparticles/Glutamic Acid Chemically Modified Electrodes. Sensor Letters.2010; 8(6):760-766.
10. Tsunoda M, Aoyama C, Nomura H. Toyoda T. Matsuki N. Funatsu T. Simultaneous determination of dopamine and 3.4-dihydroxyphenylacetic acid in mouse striatum using mixed-mode reversed-phase and cation-exchange high-performance liquid chromatography. Journal of pharmaceutical and biomedical analysis.2010;57(3):712-715.
11. Tang H, Lin P, Chan HLW, Yan F. Highly sensitive dopamine biosensors based on organic electrochemical transistors. Biosensors and Bioelectronics.2011;26(11): 4559-4563.
12. Secor KE, Timothy E. Selective amine recognition:development of a chemosensor for dopamine and norepinephrine. Organic letters.2004;6(21): 3727-3730.
13.Raoof JB, Kiani A, Ojani R, Valiollahi R. Electrochemical Determination-of Dopamine Using Banana-MWCNTs Modified Carbon Paste Electrode.2011.26(11): 4559-4563.
14. Pietrzyk A,Suriyanarayanan S, Kutner W, Maligaspe E, Zandler ME. D'Souza F. Molecularly imprinted poly [bis (2,2'-bithienyl) methane] film with built-in molecular recognition sites for a piezoelectric microgravimetry chemosensor for selective determination of dopamine. Bioelectrochemistry.2010.26(21):459-463.
15. Mahshid S, Li C, Mahshid SS, Askari M, Dolati A, Yang L. Luo S, Cai Q. Sensitive determination of dopamine in the presence of uric acid and ascorbic acid using TiO2 nanotubes modified with Pd. Pt and Au nanoparticles. Analyst.2011. 26(11):4559-4963.
16. Lin X, Zhang Y, Chen W. Wu P. Electrocatalytic oxidation and determination of dopamine in the presence of ascorbic acid and uric acid at a poly (p-nitrobenzenazo resorcinol) modified glassy carbon electrode. Sensors and Actuators B:Chemical. 2007; 122(1):309-314.
17. Li CY, Cai YJ, Yang CH. Wu CH, Wei Y, Wen TC, Wang TL. Shieh YT, Lin WC, Chen WJ. Highly sensitive and selective electrochemical determination of dopamine and ascorbic acid at Ag/Ag2S modified electrode. Electrochimica Acta.2010;56(5): 1955-1959.
18. Fengyun H, Minsheng L, Zifeng Z, Fengzhu Y, Guangyuan S. Electrochemical Behavior and Determination of Dopamine at ZnO Nanorods Intercalated Graphite Modified Electrode [J]. Chinese Journal of Applied Chemistry.2011; 25(03): 320-325.
19. Farzin L, Hosseini MRM. Simultaneous Determination of Dopamine and L-Ascorbic Acid by Modified Carbon Paste Electrode with Ni (Ⅱ) Cyclam Complex. American Journal of Analytical Chemistry.2011:2.26-99
20. Erickson CK. Review of neurotransmitters and their role in alcoholism treatment. Alcohol and Alcoholism.1996;31(suppl):5.
21. Chandra U, Swamy BEK, Gilbert O, Reddy S, Sherigara B. Determination of Dopamine in Presence of Uric Acid at Poly (Eriochrome Black t) Film Modified Graphite Pencil Electrode. American Journal of Analytical Chemistry. 2011:2:78-90
22. Atta NF, Galal A. Abu-Attia FM, Azab SM. Carbon Paste Gold Nanoparticles Sensor for the Selective Determination of Dopamine in Buffered Solutions. Journal of The Electrochemical Society.2010;157:F116-F123.
23. Abbaspour A, Valizadeh H. Khajehzadeh A. A simple, fast and cost effective method for detection and determination of dopamine in bovine serum. Anal. Methods. 2011;3(6):1405-1409.
24. Gorina AS. KolesnichenkoLS, Mikhnovich Ⅵ. Catecholamines and their metabolites in children with Asperger and Kanner syndromes. Biomed Khim.2011; 57(5):562-570.
25. Hamdy NM, El-Wakeel L, Suwailem SM. Involvement of Depressive Catecholamines as Thrombosis Risk/Inflammatory Markers in Non-Smoker, Non-Obese Congestive Heart Failure. Linked to Increased Epidermal Growth Factor-Receptor (EGF-R) Production. Indian J Clin Biochem.2011;26(2):140-145.
26. Riva R. Mork PJ. Westgaard RH, Okkenhaug Johansen T, Lundberg U Catecholamines and heart rate in female fibromyalgia patients.J Psychosom Res. 2012;72(1):51-57.
27. Vuda M, Brander L, Schroder R, Jakob SM, Takala J, Djafarzadeh S. Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs. Innate Immun.2012;18(2):217-230.
28. Peterson G. Kumar A,Gart E, Narayanan S.Catecholamines increase conjugative gene transfer between enteric bacteria. Microb Paihog.2011;57(1-2):1-8.
29. Kotecha R,Toledo-Pereyra LH. The effect of catecholamines on hepatic artery vasospasm in small-for-size syndrome liver grafts. J Surg Res.2012:172(1):77-79.
30. Holloway EL, Polumbo RA, Harrison DC. Acute circulatory effects of dopamine in patients with pulmonary hypertension. British heart journal.1975;37(5):482-485.
31. Lv H, Li A, Liu F. Ma H, Yao B. Effects of gastrodin on the dopamine system of Tourette's syndrome rat models. Biosci Trends.2009;5(2):58-62.
32. Cotzias GC, Papavasiliou PS.Gellene R. Modification of Parkinsonism—chronic treatment with L-dopa. New England Journal of Medicine.1969;280(1):337-345.
33. Paisan-Ruiz C, Guevara R. Federoff M.Hanagasi H, Sina F. Elahi E, Schneider SA. Schwingenschuh P. Bajaj N, Emre M. Early- onset L -dopa- responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6. FBXO7 and spatacsin mutations. Movement Disorders.2010;25(12):1791-1800.
34. Sagar KA. Smyth MR. Simultaneous determination of levodopa, carbidopa and their metabolites in human plasma and urine samples using LC-EC. J Pharm Biomed Anal.2000;22:613-624.
35. Karimi M. Carl JL. Loftin S. Perlmutter JS. Modified high-performance liquid chromatography with electrochemical detection method for plasma measurement of levodopa,3-O-methyldopa, dopamine, carbidopa and 3,4-dihydroxyphenyl acetic acid. J Chromatogr B Analyt Technol Biomed Life Sci.2006;836:120-123.
36. Talebpour Z, Haghgoo S, Shamsipur M.1H nuclear magnetic resonance spectroscopy analysis for simultaneous determination of levodopa. carbidopa and methyldopa in human serum and pharmaceutical formulations. Analytica Chimica Acta.2004;506:97-104.
37. Ha PT, Van Schepdael A. Hauta-Aho T, Roets E. Hoogmartens J. Simultaneous detennination of dopa and carbidopa enantiomers by capillary zone electrophoresis. Electrophoresis.2002;25(19):3404-3409.
38. Seto D. Maki T, Soh N, Nakano K. Ishimatsu R, Imato T. A simple and selective fluorometric assay for dopamine using a calcein blue-Fe2+ complex fluorophore. Talanta.2012:94:36-43.
39. Coskun A. Akkaya EU. Three-point recognition and selective fluorescence sensing of L-DOPA. Org Lett.2004;6(18):3107-3109.
40. Wu Z, Zhao H, Xue Y, He Y, Li X, Yuan Z. Colorimetric determination of melamine by pyridine-3-boronic acid modified gold nanoparticles. J Nanosci Nanotechnol 2012;12(3):2412-2416.
41.Lindwall H, Bandes J, Weinberg I. Preparation of certain brominated cinchophens. Journal of the American Chemical Society.1931;53(1):317-319.
1. Zhang L, Fang H, Xu W. Strategies in developing promising histone deacetylase inhibitors. Medicinal Research Reviews.2010;30(4):585-602.
2. Mai A, Massa S. Rotili D, Cerbara I, Valente S, Pezzi R, Simeoni S, Ragno R. Histone deacetylation in epigenetics:an attractive target for anticancer therapy. Medicinal Research Reviews.2005;25(3):261-309.
3. Itoh Y, Suzuki T, Miyata N. Isoform-selective histone deacetylase inhibitors. Curr Pharm Des.2008;14(6):529-544.
4. Carew JS, Giles FJ, Nawrocki ST. Histone deacetylase inhibitors:mechanisms of cell death and promise in combination cancer therapy. Cancer Letters.2008;269(1): 7-17.
5. Mielcarek M, Benn CL. Franklin SA. Smith DL, Woodman B, Marks PA, Bates GP. SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's disease. PLoS One.2011; 6(11): e27746.
6. Singh J, Khan M. Singh I. HDAC inhibitor SAHA normalizes the levels of VLCFAs in human skin fibroblasts from X-ALD patients and downregulates the expression of proinflammatory cytokines in Abcd1/2-silenced mouse astrocytes. Journal Of Lipid Research.2011; 52(11):2056-2069.
7. Wang L, Zou X, Berger AD, Twiss C, Peng Y, Li Y, Chiu J, Guo H, Satagopan J, Wilton A, Gerald W, Basch R, Wang Z, Osman I, Lee P. Increased expression of histone deacetylaces (HDACs) and inhibition of prostate cancer growth and invasion by HDAC inhibitor SAHA. Am J Transl Res.2009;7(1):62-71.
8. Bieliauskas AV, Weerasinghe SV, Pflum MK. Structural requirements of HDAC inhibitors:SAHA analogs functionalized adjacent to the hydroxamic acid. Bioorganic & Medicinal Chemistry Letters.2007;77(8):2216-2219.
9. Guan P, Fang H. Clinical development of histone deacetylase inhibitor romidepsin. Drug Discov Ther.2010;4(6):388-391.
10. Fiser. A.:Sali, A., Modeller: generation and refinement of homology-based protein structure models.Methods Enzymol 2003:374.461-91.
11. Wang, D. F.;Helquist, P.;Wiech, N.L.;Wiest, O.,Toward selective histone deacetylase inhibitor design:homology modeling, docking studies, and molecular dynamics simulations of human class I histone deacetylases. J Med Chem 2005; 48 (22).6936-47.
12. Morris, G. M.; Huey. R.; Lindstrom, W.; Sanner. M. F.; Belew. R. K.; Goodsell, D. S.; Olson. A. J.,AutoDock4 and AutoDockTools4:Automated docking with selective receptor flexibility. J Comput Chem 2009;30(16),2785-91.
13. Stewart, J. J., MOPAC:a semiempirical molecular orbital program. J Comput Aided Mol Des 1990,4(1),1-105.
14. Jakalian, A.; Jack, D. B.; Bayly, C. I., Fast, efficient generation of high-quality atomic charges. AM1-BCC model:Ⅱ. Parameterization and validation. J Comput Chem 2002,23(16),1623-41.
15. Moore M. Maroun J, Robert F, Natale R, Neidhart J, Dallaire B. Sisk R, Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced gastrointestinal cancer. Invest New Drugs.1993; 77(1):61-65.
16. Maroun J, Ruckdeschel J, Natale R, Morgan R, Dallaire B, Sisk R, Gyves J. Multicenter phase Ⅱ study of brequinar sodium in patients with advanced lung cancer. Cancer Chemother Pharmacol.1993;32(1):64-66.
17. Qing M, Zou G, Wang QY, Xu HY, Dong H, Yuan Z, Shi PY. Characterization of dengue virus resistance to brequinar in cell culture. Antimicrobial agents and chemotherapy.2010;54(9):3686-3695.
1. Flagstad φ, Andersen R, Wardig C, Johansson M, Breseth H, Ellegren H. Populasjonsovervaking av jerv i Skandinavia ved hjelp av DNA-analyse fra ekskrementer. NINA Rapport 165:42 pp.2006; 165.
2. Angibaud P. Van Emelen K. Arts J. Histone Deacetylase Inhibitors:A Brief Overview Of Their Role And Medicinal Chemistry. Burger's Medicinal Chemistry, Drug Discovery and Development.2010.
3. Boumber Y. Younes A. Garcia-Manero G. Mocetinostat (MGCD0103):a review of an isotype-specific histone deacetylase inhibitor. Expert opinion on investigationl drugs.2011:20(6):823-829.
4. Khaskhely N, Buglio D, Shafer J, Bollard C, Younes A. The histone deacetylase (HDAC) inhibitor entinostat (SNDX-275) targets Hodgkin lymphoma through a dual mechanism of immune modulation and apoptosis induction. Blood (ASH Annual Meeting Abstracts).2009;114:1562.
5. Piekarz RL, Frye R, Turner M. Wright JJ, Allen SL, Kirschbaum MH,Zain J, Prince HM. Leonard JP. Geskin LJ. Phase Ⅱ multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma.Journal of clinical oncology.2009:27(32):5410-5417.