3-取代吲哚酮衍生物的生物活性研究进展
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摘要
吲哚酮结构是很多药物的重要活性基团,含这类结构的化合物通常具有消炎、杀菌、抗病毒、抗高血压和抗肿瘤等生物活性。吲哚酮类化合物因具有广谱的生物活性和潜在的药效研究价值,是药物研究的热点。按照结构分类,分别为亚胺类、硫脲类、酰腙类、亚甲基类以及联氨类3-取代吲哚酮衍生物,及其在抑菌和抗肿瘤等方面的生物活性进行概述,以期为该类化合物的药物化学方面的研究提供参考价值。
Indolone is an important active group of many drugs,and compounds containing such structure usually have anti-inflammatory,bactericidal,anti-viral,anti-hypertensive,anti-tumor and other biological activities.Indolone compounds have become a hot spot in drug research because of their broad-spectrum biological activity and potential pharmacodynamic research value.Based on the structure,3-substituted indolone derivatives were divided into imines,thioureas,hydrazides,methylenes and hydrazine,and the biological activity in terms of antibacterial and antitumor were summarized.It is hoped to provide reference value for the research of these compounds on pharmacochemistry.
Indolone is an important active group of many drugs,and compounds containing such structure usually have anti-inflammatory,bactericidal,anti-viral,anti-hypertensive,anti-tumor and other biological activities.Indolone compounds have become a hot spot in drug research because of their broad-spectrum biological activity and potential pharmacodynamic research value.Based on the structure,3-substituted indolone derivatives were divided into imines,thioureas,hydrazides,methylenes and hydrazine,and the biological activity in terms of antibacterial and antitumor were summarized.It is hoped to provide reference value for the research of these compounds on pharmacochemistry.
引文
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[32]NARASIMHA R M P,NAGARAJU B,KOVVURI J,et al. Synthesis of imidazo-thiadiazole linked indolinone conjugates and evaluated their microtubule network disrupting and apoptosis inducing ability[J]. Bioorg.Chem.,2018,76:420-436.
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[34]KARUNANIDHI S,CHANDRASEKARAN B,KARPOORMATH R,et al.Pharmaceutical compounds:WIPO 2 018100 484[P].2018-06-07.
[2]王卫平,刘弋.舒尼替尼对胃肠道间质瘤患者二线治疗的临床观察[J].安徽医药,2017,21(9):1 706-1 708.
[3]曹珮,姜学军,席志军.舒尼替尼通过抑制Akt/m TOR信号通路诱导肾癌细胞自噬[J].北京大学学报,2016,48(4):584-589.
[4]周瑛.抗类风湿新药替尼达普[J].中国新药杂志,1997,6(5):341-343.
[5]AWASTHI N,HINZ S,BREKKEN R A,et al.Nintedanib,a triple angiokinase inhibitor,enhances cytotoxic therapy response in pancreatic cancer[J]. Cancer Lett.,2015,358(1):59-66.
[6]DAVIDOVICH P,AKSENOVA V,PETROVA V,et al.Discovery of novel isatin-based p53 inducers[J]. ACS Med.Chem.Lett.,2015,6(8):856-860.
[7]ELDEHNA W M,FARES M,CERUSO M,et al.Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumorassociated carbonic anhydrase isoformⅫ[J].Eur.J.Med.Chem.,2016,110:259-266.
[8]PAPE V F,TOTH S,FUREDI A,et al.Design,synthesis and biological evaluation of thiosemicarbazones,hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance[J].Eur.J.Med.Chem.,2016,117:335-354.
[9]GREENBERG W M,CITROME L.Ziprasidone for schizophrenia and bipolar disorder:a review of the clinical trials[J].CNS Drug Rev.,2007,13(2):137-177.
[10]REDDY B V S,RAJESWARI N,SARANGAPANI M,et al. Iodine-catalyzed conjugate addition of indoles onto en-1,4-dione:a novel synthesis of 3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-ones as antibacterial and antifungal agents[J].Bioorg.Med.Chem.Lett.,2011,21(21):6 510-6 514.
[11]吴亚,陈刚.吲哚-2,3-二酮衍生物抑菌活性研究进展[J].化学试剂,2015,37(8):702-706.
[12]画莉,万茂生,童张法,等.6-(呋喃-2-亚甲氨基)-2-甲基-1H-吲哚-3-羧酸乙酯的合成、表征与生物活性研究[J].化学试剂,2017,39(11):1 165-1 168.
[13]MASOUD F A,SALIMEH A,MARJAN E,et al.Synthesis of N-arylmethyl substituted indole derivatives as new antiplatelet aggregation agents[J]. Iran. J. Pharm. Res.,2014,13:35-42.
[14]ELDEHNA W M,FARES M,IBRAHIM H S,et al.Synthesis and cytotoxic activity of biphenylurea derivatives containing indolin-2-one moieties[J]. Molecules,2016,21(6):762-772.
[15]KUMAR M,NARASIMHAN B,RAMASAMY K,et al.Synthesis,antimicrobial and cytotoxic evaluation of 4-(1-aryl-5-halo-2-oxo-1, 2-dihydro-indol-3-ylideneamino)-N-substituted benzene sulfonamides[J]. Arab. J.Chem.,2017,10:2 845-2 852.
[16]KULKARNI A A,WANKHEDE S B,DHAWALE N D,et al. Synthesis,characterization and biological behavior of some Schiff's and Mannich base derivatives of Lamotrigine[J].Arab.J.Chem.,2017,10:184-189.
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[18]ALI A Q,TEOH S G,SALHIN A,et al.Synthesis of isatin thiosemicarbazones derivatives:in vitro anti-cancer,DNA binding and cleavage activities[J].Spectrochim.Acta A,2014,125:440-448.
[19]TEHRANI K H M E,HASHEMI M,HASSAN M,et al.Synthesis and antibacterial activity of Schiff bases of 5-substituted isatins[J]. Chinese Chem. Lett.,2016,27(2):221-225.
[20]MANIKANDAN A,MOHARIL P,SATHISHKUMAR M,et al. Therapeutic investigations of novel indoxyl-based indolines:a drug target validation and structure-activity relationship of angiotensin-converting enzyme inhibitors with cardiovascular regulation and thrombolytic potential[J].Eur.J.Med.Chem.,2017,141:417-426.
[21]XU Z,ZHANG S,SONG X F,et al.Design,synthesis and in vitro anti-mycobacterial evaluation of gatifloxacin-1H-1,2,3-triazole-isatin hybrids[J]. Bioorg. Med. Chem.Lett.,2017,27(16):3 643-3 646.
[22]SONG G Q,WANG W M,LI Z S,et al.First identification of isatin-β-thiosemicarbazones as novel inhibitors of new delhi metallo-β-lactamase-1:chemical synthesis,biological evaluation and molecular simulation[J].Chinese Chem.Lett.,2018,29(6):899-902.
[23]LIAN Z M,SUN J,ZHU H L.Design,synthesis and antibacterial activity of isatin derivatives as Fts Z inhibitors[J].J.Mol.Struct.,2016,1 117:8-16.
[24]ALMUTAIRI M S,ZAKARIA A S,IGNASIUS P P,et al. Synthesis,spectroscopic investigations,DFT studies,molecular docking and antimicrobial potential of certain new indole-isatin molecular hybrids:experimental and theoretical approaches[J]. J. Mol. Struct.,2018,1 153:333-345.
[25]ARSHAD M,JADOON M,IQBAL Z,et al. Synthesis,molecular structure,quantum mechanical studies and urease inhibition assay of two new isatin derived sulfonylhydrazides[J].J.Mol.Struct.,2017,1 133:80-89.
[26]MAHMOUD F A,WAGDY M E,ALESSIO N,et al.Novel hydrazido benzenesulfonamides-isatin conjugates:synthesis,carbonic anhydrase inhibitory activity and molecular modeling studies[J]. Eur. J. Med. Chem.,2018,157:28-36.
[27]IBRAHIM H S,ABOU-SERI S M,ISMAIL N S M,et al.Bis-isatin hydrazones with novel linkers:synthesis and biological evaluation as cytotoxic agents[J]. Eur. J. Med.Chem.,2016,108:415-422.
[28]SONG Z,CHEN C P,LIU J,et al.Design,synthesis,and biological evaluation of(2E)-(2-oxo-1,2-dihydro-3Hindol-3-ylidene)acetate derivatives as anti-proliferative agents through ROS-induced cell apoptosis[J]. Eur. J.Med.Chem.,2016,124:809-819.
[29]SHARMA P,THUNNURI D,REDDY T S,et al. New(E)-1-alkyl-1H-benzo[d]imidazol-2-yl)methylene)indolin-2-ones:synthesis,in vitro cytotoxicity evaluation and apoptosis inducing studies[J]. Eur. J. Med. Chem.,2016,122:584-600.
[30]ELDEHNA W M,ABO-ASHOUR M F,NOCENTINI A,et al.Novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino)benzenesulfonamides:synthesis,carbonic anhydrase inhibitory activity,anticancer activity and molecular modelling studies[J].Eur.J.Med.Chem.,2017,139:250-262.
[31]WANG J B,YUN D,YAO J L,et al. Design,synthesis and QSAR study of novel isatin analogues inspired Michael acceptor as potential anticancer compounds[J].Eur.J.Med.Chem.,2018,144:493-503.
[32]NARASIMHA R M P,NAGARAJU B,KOVVURI J,et al. Synthesis of imidazo-thiadiazole linked indolinone conjugates and evaluated their microtubule network disrupting and apoptosis inducing ability[J]. Bioorg.Chem.,2018,76:420-436.
[33]WANG G C,CHEN M,QIU J,et al. Synthesis,in vitro alpha-glucosidase inhibitory activity and docking studies of novel chromone-isatin derivatives[J]. Bioorg. Med.Chem.Lett.,2018,28(2):113-116.
[34]KARUNANIDHI S,CHANDRASEKARAN B,KARPOORMATH R,et al.Pharmaceutical compounds:WIPO 2 018100 484[P].2018-06-07.