新型氧杂蒽和呋喃衍生物的合成及其抗肿瘤活性研究
|
摘要
蒽醌类药物是非常重要的一类抗肿瘤药物,具有抗瘤谱广,临床疗效好等优点。其中,多柔比星、柔红霉素、表柔比星和米托蒽醌等蒽醌类化合物都是临床上常用抗肿瘤药,但此类药物随着剂量的增加,伴有骨髓抑制、心脏毒性等副作用。因此,以降毒增效为目的的蒽醌类似物的研究工作具有重要意义。
抗肿瘤药物放线菌素D是氧杂蒽类似物,具有非常好的临床疗效,通过文献调研又发现以氧原子替代蒽醌结构中的羰基可以降低其对心脏的毒性,并保留其抗肿瘤活性,所以研究新型氧杂蒽类衍生物有重要意义。本论文以放线菌素D为参照物,设计、合成了162个目标化合物,其中二苯[a,j]氧杂蒽类化合物130个,二萘并[2,1-b：1',2'-d]呋喃衍生物32个,经IR、1H NMR、13C NMR和HR-MS等波谱学方法确认了162个目标化合物的结构。以As203作为阳性对照药,利用MTT法测定了其中91个具有代表性化合物对人肝癌细胞(SK-HEP-1细胞,HepG2细胞,SMMC-7721),人急性早幼粒白血病细胞(NB4细胞),人宫颈癌细胞(HeLa细胞)等5种肿瘤细胞的抗肿瘤活性。
在130个二苯[a,j]氧杂蒽类化合物中,共有117个新化合物和13个已知化合物,对于以上13个已知化合物均采用无溶剂的绿色合成方法进行制备。
32个二萘并[2,1-b：1',2'-d]呋喃衍生物分别为17个6,8-二取代二萘并[2,1-b：1',2'-d]呋喃类化合物,14个3,11-二取代二萘并[2,1-b：1',2'-d]呋喃类化合物和1个二萘并[2,1-b：1',2'-d]呋喃母体化合物,这32个化合物中,28个为新化合物,4个为已知化合物。
对二苯[a,j]氧杂蒽类化合物的抗肿瘤活性研究表明：(1)在母体化合物的3和11位引入适合的取代基可使此类化合物抗肿瘤活性明显增强；(2)N3(N11)上引入一个烷基时,随着烷基的体积增大,化合物的抗肿瘤活性减弱；(3)N3(N11)上引入两个烷基时,二乙基衍生物抗肿瘤活性强于二甲基衍生物；(4)二苯并氧杂蒽母体14位有对卤苯基取代时,抗肿瘤活性最好,14位有邻卤苯基取代时,抗肿瘤活性较弱；(5)此类化合物的抗肿瘤活性可能受3、11和14位的取代基共同影响；化合物35、37、38、40、30、31和32对白血病NB4细胞的IC50值分别为0.82、0.96、2.06、2.38、3.08、4.12和4.01μM,均小于阳性药As2O3的5.01μM,具有深入研究的意义。
对6,8-二取代二萘并[2,1-b：1',2'-d]呋喃衍生物抗肿瘤活性研究表明：目标物154、155、159和162对肿瘤细胞的抑制作用较强,其IC50值都小于20μM(母体化合物148的IC50值大于50μM),说明在母体化合物148的6位和8位引入取代基,可增强此类化合物的抗肿瘤活性。
对3,11-二取代二萘并[2,1-b：1',2'-d]呋喃衍生物抗肿瘤活性研究表明：化合物161对肝癌细胞SMMC-7721的IC50值为0.57μM小于阳性对照品As2O3的9.13μM,另外,化合物178对NB4的IC50值也达到了5.07μM,这两个化合物需要进行进一步的抗肿瘤活性研究。可以看出在二萘并[2,1-b：1',2'-d]呋喃化合物148的3位和11位引入适合的取代基,可明显增强此类化合物的抗肿瘤活性。
本论文以抗肿瘤活性的较好的化合物37和38为代表,利用流式细胞法研究了它们对HeLa细胞的抑制机制。研究结果表明：化合物37和38对肿瘤细胞的抑制作用主要是通过诱导细胞凋亡产生的。
Anthraquinone drugs are very important antitumor medicines, which exhibit the advantages of wide antitumor spectrum and good clinical practice. Some anthraquinone compounds including doxorubicin, daunorubicin, doxorubicin and mitoxantrone are widely used as antitumor drugs clinically. However, these drugs may lead to bone marrow suppression, cardiac toxicity and other side effects as the dose increases to a relatively high level. Therefore, it is of significance to design analogues of anthraquinone with less toxicity.
As an analogue of xanthenes, Dactinomycin D is an excellent antitumor drug, and it is found from literature that the toxicity of anthraquinone compound to the heart can be reduced by replacing the carbonyl group with oxygen atom with the antitumor activity kept unchanged, so it is of great importance to design new types of xanthenes derivatives. In this thesis,162target compounds including130dibenzo[a,j]xanthenes compounds and32dinaphtho[2,1-b:1'.2'-d]furan derivatives were designed and synthesized, according to the structure of dactinomycin D. And the structures of all the compounds were characterized and identified by1H NMR,13C NMR, HR-MS and IR spectra. Using As2O3as the positive control, antitumor activities of91representative compounds were evaluated on carcinoma cell lines (SK-HEP-1, HepG2and SMMC-7721cells), acute promyelocytic leukemia NB4cells and uterine cervix cancer HeLa cells.
Among130dibenzene[a,j]xanthenes compounds, there are117new compounds and13known compounds, and all the known derivatives were prepared by solvent-free green synthesis method.
32derivatives of furan include seventeen6,8-disubstituted dinaphtho[2,1-b:1',2'-d]furan compounds, fourteen3,11-disubstituted dinaphtho[2,1-b:1',2'-d]furan derivatives and one parent compound dinaphtho[2,1-b:1',2'-d]furan. Among these32compounds, there are twenty-eight new compounds and four known compounds.
Through the study on the antitumor activities of dibenzo[aj]xanthenes compounds, the following conclusions can be drawn:(1) Antitumor activities of the parent compounds can be significantly enhanced after3and11positions of the compounds are substituted with proper groups;(2) As only an alkyl group is introduced on the N3(N11) atoms, antitumor activities decrease with the increasing of the size of the alkyl group;(3) When two alkyl groups are introduced on the N3(N11) atoms, the antitumor activities of diethyl derivatives are stronger than those of dimethyl ones;(4) When14position is substituted with p-halophenyl groups, the antitumor activity of the derivatives is the strongest, However, when14position is substituted with o-halophenyl groups, the antitumor activity become weaker;(5) The antitumor activities of these compounds may be affected by substituent groups on3,11and14positions synergistically. The IC50values of compounds35,37,30,31and32for NB4cell are0.82,0.96,3.08,4.12and4.01μM, respectively. Their IC50values are less than5.01μM of positive drug As2O3, deserving to be studied furtherly.
Through the study on the antitumor activities of6,8-disubstituted dinaphtho[2,1-b:1',2'-d]furan, it is found that compounds154,155,159and162have stronger inhibitive effects on tumor cells and their IC50values are less than20μM (the IC50value of the parent compound148exceeds50μM). The results show that antitumor activities of this kind of compounds can be enhanced when6and8positions are substituted.
Through the study on the antitumor activities of3,11-disubstituted dinaphtho[2,1-b:1',2'-d|furan derivatives, it is found that the IC50value of compound161is0.57μM for SMMC-7721cell, which is less than9.13μM of positive drug As2O3. In addition, the IC50value of compound178also reaches5.07μM for NB4cell. Further investigations need to be carried out on the antitumor activities of the two compounds. The results indicate that the antitumor activities of dinaphtho[2,1-b:1',2'-d]furan compound148can be improved obviously when3and11positions are properly substituted.
Taking compounds37and38as the representative compounds with better antitumor activities, the mechanism of inhibiting on HeLa cell was studied by the flow cytometry analysis method in this thesis. The results show that the inhibitory effects of compounds37and38on tumor cells are realized mainly by inducing cell apoptosis.
抗肿瘤药物放线菌素D是氧杂蒽类似物,具有非常好的临床疗效,通过文献调研又发现以氧原子替代蒽醌结构中的羰基可以降低其对心脏的毒性,并保留其抗肿瘤活性,所以研究新型氧杂蒽类衍生物有重要意义。本论文以放线菌素D为参照物,设计、合成了162个目标化合物,其中二苯[a,j]氧杂蒽类化合物130个,二萘并[2,1-b：1',2'-d]呋喃衍生物32个,经IR、1H NMR、13C NMR和HR-MS等波谱学方法确认了162个目标化合物的结构。以As203作为阳性对照药,利用MTT法测定了其中91个具有代表性化合物对人肝癌细胞(SK-HEP-1细胞,HepG2细胞,SMMC-7721),人急性早幼粒白血病细胞(NB4细胞),人宫颈癌细胞(HeLa细胞)等5种肿瘤细胞的抗肿瘤活性。
在130个二苯[a,j]氧杂蒽类化合物中,共有117个新化合物和13个已知化合物,对于以上13个已知化合物均采用无溶剂的绿色合成方法进行制备。
32个二萘并[2,1-b：1',2'-d]呋喃衍生物分别为17个6,8-二取代二萘并[2,1-b：1',2'-d]呋喃类化合物,14个3,11-二取代二萘并[2,1-b：1',2'-d]呋喃类化合物和1个二萘并[2,1-b：1',2'-d]呋喃母体化合物,这32个化合物中,28个为新化合物,4个为已知化合物。
对二苯[a,j]氧杂蒽类化合物的抗肿瘤活性研究表明：(1)在母体化合物的3和11位引入适合的取代基可使此类化合物抗肿瘤活性明显增强；(2)N3(N11)上引入一个烷基时,随着烷基的体积增大,化合物的抗肿瘤活性减弱；(3)N3(N11)上引入两个烷基时,二乙基衍生物抗肿瘤活性强于二甲基衍生物；(4)二苯并氧杂蒽母体14位有对卤苯基取代时,抗肿瘤活性最好,14位有邻卤苯基取代时,抗肿瘤活性较弱；(5)此类化合物的抗肿瘤活性可能受3、11和14位的取代基共同影响；化合物35、37、38、40、30、31和32对白血病NB4细胞的IC50值分别为0.82、0.96、2.06、2.38、3.08、4.12和4.01μM,均小于阳性药As2O3的5.01μM,具有深入研究的意义。
对6,8-二取代二萘并[2,1-b：1',2'-d]呋喃衍生物抗肿瘤活性研究表明：目标物154、155、159和162对肿瘤细胞的抑制作用较强,其IC50值都小于20μM(母体化合物148的IC50值大于50μM),说明在母体化合物148的6位和8位引入取代基,可增强此类化合物的抗肿瘤活性。
对3,11-二取代二萘并[2,1-b：1',2'-d]呋喃衍生物抗肿瘤活性研究表明：化合物161对肝癌细胞SMMC-7721的IC50值为0.57μM小于阳性对照品As2O3的9.13μM,另外,化合物178对NB4的IC50值也达到了5.07μM,这两个化合物需要进行进一步的抗肿瘤活性研究。可以看出在二萘并[2,1-b：1',2'-d]呋喃化合物148的3位和11位引入适合的取代基,可明显增强此类化合物的抗肿瘤活性。
本论文以抗肿瘤活性的较好的化合物37和38为代表,利用流式细胞法研究了它们对HeLa细胞的抑制机制。研究结果表明：化合物37和38对肿瘤细胞的抑制作用主要是通过诱导细胞凋亡产生的。
Anthraquinone drugs are very important antitumor medicines, which exhibit the advantages of wide antitumor spectrum and good clinical practice. Some anthraquinone compounds including doxorubicin, daunorubicin, doxorubicin and mitoxantrone are widely used as antitumor drugs clinically. However, these drugs may lead to bone marrow suppression, cardiac toxicity and other side effects as the dose increases to a relatively high level. Therefore, it is of significance to design analogues of anthraquinone with less toxicity.
As an analogue of xanthenes, Dactinomycin D is an excellent antitumor drug, and it is found from literature that the toxicity of anthraquinone compound to the heart can be reduced by replacing the carbonyl group with oxygen atom with the antitumor activity kept unchanged, so it is of great importance to design new types of xanthenes derivatives. In this thesis,162target compounds including130dibenzo[a,j]xanthenes compounds and32dinaphtho[2,1-b:1'.2'-d]furan derivatives were designed and synthesized, according to the structure of dactinomycin D. And the structures of all the compounds were characterized and identified by1H NMR,13C NMR, HR-MS and IR spectra. Using As2O3as the positive control, antitumor activities of91representative compounds were evaluated on carcinoma cell lines (SK-HEP-1, HepG2and SMMC-7721cells), acute promyelocytic leukemia NB4cells and uterine cervix cancer HeLa cells.
Among130dibenzene[a,j]xanthenes compounds, there are117new compounds and13known compounds, and all the known derivatives were prepared by solvent-free green synthesis method.
32derivatives of furan include seventeen6,8-disubstituted dinaphtho[2,1-b:1',2'-d]furan compounds, fourteen3,11-disubstituted dinaphtho[2,1-b:1',2'-d]furan derivatives and one parent compound dinaphtho[2,1-b:1',2'-d]furan. Among these32compounds, there are twenty-eight new compounds and four known compounds.
Through the study on the antitumor activities of dibenzo[aj]xanthenes compounds, the following conclusions can be drawn:(1) Antitumor activities of the parent compounds can be significantly enhanced after3and11positions of the compounds are substituted with proper groups;(2) As only an alkyl group is introduced on the N3(N11) atoms, antitumor activities decrease with the increasing of the size of the alkyl group;(3) When two alkyl groups are introduced on the N3(N11) atoms, the antitumor activities of diethyl derivatives are stronger than those of dimethyl ones;(4) When14position is substituted with p-halophenyl groups, the antitumor activity of the derivatives is the strongest, However, when14position is substituted with o-halophenyl groups, the antitumor activity become weaker;(5) The antitumor activities of these compounds may be affected by substituent groups on3,11and14positions synergistically. The IC50values of compounds35,37,30,31and32for NB4cell are0.82,0.96,3.08,4.12and4.01μM, respectively. Their IC50values are less than5.01μM of positive drug As2O3, deserving to be studied furtherly.
Through the study on the antitumor activities of6,8-disubstituted dinaphtho[2,1-b:1',2'-d]furan, it is found that compounds154,155,159and162have stronger inhibitive effects on tumor cells and their IC50values are less than20μM (the IC50value of the parent compound148exceeds50μM). The results show that antitumor activities of this kind of compounds can be enhanced when6and8positions are substituted.
Through the study on the antitumor activities of3,11-disubstituted dinaphtho[2,1-b:1',2'-d|furan derivatives, it is found that the IC50value of compound161is0.57μM for SMMC-7721cell, which is less than9.13μM of positive drug As2O3. In addition, the IC50value of compound178also reaches5.07μM for NB4cell. Further investigations need to be carried out on the antitumor activities of the two compounds. The results indicate that the antitumor activities of dinaphtho[2,1-b:1',2'-d]furan compound148can be improved obviously when3and11positions are properly substituted.
Taking compounds37and38as the representative compounds with better antitumor activities, the mechanism of inhibiting on HeLa cell was studied by the flow cytometry analysis method in this thesis. The results show that the inhibitory effects of compounds37and38on tumor cells are realized mainly by inducing cell apoptosis.
引文
[1]GUTIERREZ M E, KUMMAR S, GIACCONE G. Next Generation Oncology Drug Development:Opportunities and Challenges[J]. Nat Rev Clin Oncol,2009, 6(5):259-265.
[2]甄永苏.抗肿瘤药物研究与开发[M].北京：化学工业出版社,2004：39-30.
[3]KROEP J R, GELDERBLOM M. Diflomotecan, Apromisingho Mocamptothecin for Cancer Therapy[J], Expert Opin Investig Drugs,2009,18(1):69-75.
[4]JORDAN M A, WILSON L. Microtubules as A Target for Anticancer Drugs [J]. Nat Rev Cancer.2004,4(4):253-265.
[5]DUMONTET C, JORDAN M A, LEE F F Y, et al. Ixabepilone:Targeting BIII-Tubulin Expression in Taxane-Resistant Malignancies[J]. Mol Cancer Ther, 2009,8(1):17-25.
[6]CIGLER T, VAHDAT L T. Eribulin Mesylate for The Treatment of Breast Cancer[J]. Expert Opin Pharmaco,2010,11(9):1587-1593.
[7]THOMAS BOYLE F, COSTELLO G F. Cancer Therapy:A Move to The Molecular Level[J]. Chem Soc Rev.1998,27(1):251-261.
[8]ZHOU J B, GOH B C, Albert D H, et al. ABT-869, A Promising Multi-Targeted Tyrosine Kinase Inhibitor:from Bench to Bedside[J]. J Hematol Oncol,2009,2: 33.
[9]O'HARE T, SHAKESPEARE W C, ZHU X T, et al. AP24534, A Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits The T315I Mutant and Overcomes Mutation-Based Resistance[J]. Cancer Cell,2009,16(5):401-412.
[10]赵玉娜,邢爱敏.酪氨酸蛋白激酶抑制剂Ruxolitinib[J].药学进展,2010,34(11)：523-524.
[II]XIE H, LIN L P, TONG L J, et al. AST-6, A Novel Irreversible Inhibitor of The Epidermal Growth Factor Receptor 1 and 2, Inhibits Tumor Growth Both In Vitro And In Vivo[J]. Mol Cancer Ther.2009,8(12):C50.
[12]谭芬来,张力,赵琼,等,国家一类新药盐酸埃克替尼的药理与临床评价[J].中国新药杂志,2009,18(18)：1691-1694.
[13]LEBOWITZ PF, PRENDERGAST GC. Non-Ras Targets of Farnesyltransferase Inhibitors:Focus on Rho[J].Oncogene,1998,17(11):1439-1445.]
[14]SEBTI S M, HAMILTON A D. New Approaches to Anticancer Drug Design Based on The Inhibition of Farnesyltransferase. Drug Discov Today,1998,3(1): 26-33.
[15]SEPP-LORENZINO L, MA Z, RANDS E, et al. A Peptidomimetic Inhibitor of Farnesyl:Protein Transferase Blocks The Anchorage-Dependent and Independ-ent Growth of Human Tumor Cell Lines[J]. Cancer Res,1995,55(22):5302-5309.
[16]XIE J J, XU L Y, XIE Y M, et al. Roles of Ezrin in The Growth and Invasiveness of Esophageal Squamous Carcinoma Cells[J]. Int J Cancer.2009,124(11):2549-2558.
[17]INFANTE J R, FECHER L A, NALLAPAREDDY S, et al. Safety and Efficacy Results from The First-In-Human Study of The Oral MEK 1/2 Inhibitor GSK1120212[J]. J Clin Oncol,2010,28(15):2503-2511.
[18]LEE L, NIU H F, RUEGER R, et al. The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of CH4987655 in Healthy Volunteers:Target Suppression Using A Biomarker[J]. Clin Cancer Res,2009, 15(16):7368-7377.
[19]PEROLLET C, HAN ZC, SAVON A C, et al. Platelet Factor 4 Modulates Fibroblast Growth Factor 2 (FGF-2) Activity and Inhibits FGF-2 Dimerization[J]. Blood,1998,91:3289-3299.
[20]MARTIN DC, SANCHEZ-SWEATMAN OH, HO A T, et al. Transgenic TIMP-1 Inhibits Simian Virus 40 T Antigen-Induced Hepatocarcinogenesis by Impairm-ent of Hepatocellular Proliferation and Tumor Angiogenesis[J]. Lab Invest,1999, 79(2):225-234.
[21]MOUSA SA. Mechanisms of Angiogenesis in Vascullar Disorders:Potential Therapeutic Targets[J]. Drugs Fut,1998,23(1):51-60.
[22]SCHLUMBERGER M J, ELISEI R, BASTHOLT L, et al. Phase II Study of Safety and Efficacy of Motesanib in Patients with Progressive or Symptomatic, Advanced or Metastatic Medullary Thyroid Cancer[J]. J Clin Oncol,2009, 27(23):3794-3801.
[23]LEVITZKI A. Signal-Transduction Therapy. A Novel Approach to Disease Man-agement[J]. Eur J Biochem,1994,226(1):1-13.
[24]LEVITZKI A. Protein Tyrosine Kinase Inhibitors as Therapeutic Agents[J]. Top Curr Chem,1998,211(1):1-15.
[25]WHITECHEAD R P, RANKIN C, HOFF P M G, et al. Phase Ⅱ Trial of Romidepsin (NSC-630176) in Previously Treated Colorectal Cancer Patients with Advanced Disease:A Southwest Oncology Group Study(S0336)[J]. Invest New Drugs,2009,27(5):469-475.
[26]FLORES I, BLASCO MA. The Role of Telomeres and Telomerase in Stem Cell Aging[J]. FEBS Lett,2010,584(17):3826-3830.
[27]CHEN W, CHEN SM, YU Y, et al. Telomerase Inhibition Alters Telomere Maintenance Mechanisms in Laryngeal Squamous Carcinoma Cells[J]. J Lary-ngol Otol,2010,124(7):778-783.
[28]FENG J, FUNK W D, WANG S S, et al. The RNA Component of Human Telomerase. Science,1995,269(5228):1236-1241.
[29]SUMI M, TAUCHI T, SASHIDA G, et al. A G-Quadruplex-Interactive Agent, Telomestatin (Sot-095), Induces Telomere Shortening with Apoptosis and Enhance Schemosensitivity in Acute Myeloid Leukemia[J]. Int J Oncol,2004, 24(6):1481-1487.
[30]ZHOU J M, ZHU X F, LU YJ, et al. Senescence and Telomere Shortening Induced by Novel Potent G-Quadruplex Interactive Agents, Quindoline Derivatives, in Human Cancer Cell Lines[J]. Oncogene,2006,25(4):503-511.
[31]TURK D, SZAKACS G. Relevance of Multidrug Resistance in The Age of Targ-eted Therapy [J]. Curr Opin Drug Dis Dev,2009,12(2):246-252.
[32]TEODORI E, DEI S, QUIDU P, et al. Design, Synthesis, and In Vitro Activity of Catamphiphilic Reverters of Multidrug Resistance:Discovery of A Selective, Highly Efficacious Chemosensitizer with Potency in The Nanomolar Range[J]. J Med Chem,1999,42(10):1687-1697.
[33]VOLM M. Multidrug Resistance and Its Reversal[J]. Anticancer Res,1998, 18(4C):2905-2917.
[34]巫凤娟,杨臻峥,孙大柠.抗癌药ABT-263[J].药学进展,2009,33(7)：330-332.
[35]BILLAM M, SOBOLEWSKI M D, DAVIDSON N E. Effects of A Novel DNA Methyltransferase Inhibitor Zebularine on Human Breast Cancer Cells[J]. Breast Cancer Res Treat,2010,120(3):581-592.
[36]SHANGARY S, WANG S. Small-molecule Inhibitors of The MDM2-P53 Protein-Protein Interaction to Reactivate P53 Function:A Novel Approach for Cancer Therapy[J]. Annu Rev Pharmacol Toxicol,2009,49(1):223-241.
[37]XUAN Y, HU X. Naturally-occurring Shikonin Analogues-A Class of Necropto-tic Inducers That Circumvent Cancer Drug Resistance[J]. Cancer Lett.2009, 274(2):233-242.
[38]ASHIMORI N, ZEITLIN B D, ZHANG Z C, et al. TW-37, A Small-Molecule Inhibitor of Bcl-2, Mediates S-Phase Cell Cycle Arrest and Suppresses Head and Neck Tumor Angiogenesis[J]. Mol Cancer Ther,2009,8(4):893-903.
[39]PIERCE J N, STEIN S. Multiple Diversity with Nonindependent Fading[J]. Proceedings of the IRE,1960,48(1):89-104.
[40]FRIEDMAN H, CEGLOWSKI WS. Leukemia Virus-Induced Immuno-suppression Ⅷ. Rapid Depression of In Vitro Leukocyte Migration after Infection of Mice with Friend Leukemia Virus[J]. J Immunol,1971,107(6): 1673-1681.
[41]董倩,姜达.实体瘤诱导分化治疗研究现状[J].肿瘤学杂志,2004,10(6)：443-446.
[42]郑小卫.抗肿瘤药物研究新进展[J].四川生理科学杂志,2007,29(4)：170-173.
[43]MINOTTI G, MENNA P, SALVATORELLI E, et al. Anthracyclines:Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity[J]. Pharmacol Rev.2004,56(2):185-229.
[44]LAUNCHBURY A P, HABBOUBI N. Epirubicin and Doxorubicin:A Comparis-on of Their Characteristics, Therapeutic Activity and Toxicity[J]. Cancer Treat Rev.1993,19(3):197-228.
[45]BONADONNA G, GIANNI L, SANTORO A, et al. Drugs Ten Years Later: Epirubicin[J]. Ann Oncol.1993,4(5):359-369.
[46]TAATJES D J, FENICK D J, KOCH T H. Nuclear Targeting and Nuclear Retention of Anthracycline-Formaldehyde Conjugates Implicates DNA Covalent Bonding in the Cytotoxic Mechanism of Anthracyclines[J]. Chem Res Toxicol, 1999,12(7):588-596.
[47]MORO S, BERETTA G L, DAL BEN D, et al. Interaction Model for Anthracycline Activity Against DNA Topoisomerase Ⅱ[J]. Biochemistry,2004, 43(23):7503-7513.
[48]ANDFIVON W, SAUCIER J M, AUCLAIR C, et al. Enhanced Topoisomerase II-Induced DNA Breaks and Free Radical Production by A New Anthracycline with Potent Antileukemic Activity[J]. Leuk Res,1996,20(2):119-126.
[49]SUN I L, CRANE F L, LOW H, et al. Inhibition of Plasma Membrane NADH Dehydrogenase by Adriamycin and Related Anthracycline Antibiotics [J]. J Bioenerg Biomembr.1984,16(3):209-221.
[50]阴键,郭力芳.中药现代研究与临床应用[M].北京：学苑山版社,1993：435.
[51]胡凯文,侯丽,陈信义,等.大黄酸/大黄素抗多药耐药肿瘤细胞研究[J].中国中医基础药学杂志,1998,4(11)：19-20.
[52]SU H Y, CHERNG S H, CHEN C C, et al. Emodin Inhibits The Mutagenicity and DNA Adducts Induced by 1-Nitropyrene. Mutat Res,1995,329(6):205-212.
[53]ZHANG L, CHANGC J, BACUS SS, et al. Suppressed Transformation and Induced Differentiation of HER-2/neu-overexpressing Breast Cancer Cells by Emodin[J]. Cancer Res,1995,55:3890-3896.
[54]SAFAEI-GHOMI J, GHASEMZADEH M A. Zinc Oxide Nanoparticles, A Highly Efficient and Readily Recyclable Catalyst for the Synthesis of XanthenesfJ]. Chin Chem Lett,2012,23(11):1225-1229.
[55]ZARE A, MOOSAVI-ZARE A R, MERAJODDIN M, et al. Ionic Liquid Triethylamine-Bonded Sulfonic Acid [[Et3N-SO3H]Cl] as A Novel, Highly Efficient and Homogeneous Catalyst for the Synthesis of β-Acetamido Ketones, 1,8-Dioxo-Octahydroxanthenes and 14-Aryl-14H-Dibenzo[a,j]Xanthenes[J]. J Mol Liq,2012,167:69-77.
[56]SHARMA M, MANOHAR S, RAWAT D S. Lewis Acid Catalyzed Synthesis of 1-Aryl-1,2-Dihydronaphtho[1,2-e][1,3]Oxazin-3-Ones under Solvent Free Conditions:A Mechanistic Approach[J]. J Heterocyclic Chem,2012,49(3): 589-595.
[57]GHASSAMIPOUR S, SARDARIAN A R. Facile Catalyzed Preparation of 14-Aryl- or -Alkyl-14-H-Dibenzo[a,j]Xanthenes by Dodecylphosphonic Acid and Dodecylsulfamic Acid:Environmentally Benign Methods[J]. J Heterocyclic Chem,2012,49(3):669-674.
[58]Prasad D, Nath M. PEG-SO3H Catalyzed, Environmentally Benign Synthesis of 14-Aryl-14H-Dibenzo[aj]Xanthenes under Solvent-Free Conditions[J]. Catal Sci Technol,2012,2(1):93-96.
[59]MOHAMMED N N G, PANDHARPATTE M S. Microwave Promoted, Perch-Loric Acid-Catalyzed One-Pot Synthesis of Xanthene Derivatives under Solvent-Free Conditions[J]. Der Pharma Chemica,2011,3(1):65-71.
[60]SOLEIMANI E, KHODAEI M M, KOSHVANDI A T K. The Efficient Synthesis of 14-Alkyl or Aryl 14H-Dibenzo[α,j]Xanthenes Catalyzed by Bismuth(Ⅲ) Chloride under Solvent-Free Conditions [J]. Chinese Chem Lett,2011,22(8): 927-930.
[61]TABATABAEIAN K, KHORSHIDI A, MAMAGHANI M, et al. Facile and Efficient Method for The Synthesis of 14-Substituted-14-H-Dibenzo[α,j] Xanthenes Catalyzed by Ruthenium Chloride Hydrate as A Homogeneous Catalyst[J]. Synthetic Commun,2011,41(10):1427-1434.
[62]WANG Bo, LI Pinhua, ZHANG Yicheng, et al. FeCl3-Catalyzed Condensation of 2-Naphthol and Aldehydes under Solvent-Free Reaction Conditions. An Efficient and Green Alternative for the Synthesis of 14-Aryl(Alkyl)-14H-Dibenzo[α, j]Xanthenes[J]. Chinese J Chem,2010,28(12):2463-2468.
[63]KARIMI-JABERI, Z, KESHAVARZI M. Efficient One-Pot Synthesis of 14-Substituted-14H-Dibenzo[a,j]Xanthenes Using Boric Acid under Solvent-Free Conditions[J]. Chinese Chem Lett,2010,21(5):547-549.
[64]Kumar A, Sharma S, Maurya R A, et al. Diversity Oriented Synthesis of Benzox-anthene and Benzochromene Libraries via One-Pot, Three-Component Reactions and Their Anti-proliferative Activity [J]. J Comb Chem,2010,12(1):20-24.
[65]Kumar R, Nandi G C, Verma R K, et al. A Facile Approach for the Synthesis of 14-Aryl- or Alkyl-14H-Dibenzo[α,j]Xanthenes under Solvent-Free Condition[J]. Tetrahedron Lett,2010,51(2):442-445.
[66]KUMAR C N S S P, SRINIVAS C, SADHU P S, et al. Efficient Synthesis of 14-Substituted-14- H-Dibenzo[α,j]Xanthenes Using Silica Supported Sodium Hydrogen Sulfate or Amberlyst-15 Catalyst[J]. J Heterocyclic Chem,2009, 46(5):997-999.
[67]JHA A, BEAL J. Convenient Synthesis of 12H-Benzo[a]Xanthenes from 2-Tetra-lone[J]. Tetrahedron Lett.2004,45(49):8999-9001.
[68]OLYAEI A, GESMATI F, SADEGHPOUR M, et al. Synthesis of Novel Anil-Like Compounds from Heteroaryl Amines, Naphthols, and Triethylorthoforma-te Under Solvent-Free Conditions[J]. Synth Commun,2012,42(11):1650- 1660.
[69]ZHANG X, LIU Q, SON A, et al. Photophysical Properties of Dibenzofluoresce-in and The Presence of its Tautomers or Prototropic Forms in Organic Solvents[J]. Photochem Photobiol Sci,2008,7(3):299-302.
[70]Banihashemi A, Rahmatpour A. First Synthesis of 1,1,4,4-Tetrakis(2-hydroxyp henyl)butane Type Compounds from Condensation of p-Substituted Phenol Derivatives with 2,5-Dimethoxytetrahydrofuran in Trifluoroacetic Acid[J]. J Chem Res Synop,1999,6:390-391.
[71]史达清,庄启亚,陈景,等.水溶剂中芳醛与5,5-二甲基-1,3-坏己二酮的反应[J].有机化学,2003,23(7)：694-696.
[72]SHUKLA G, VERMA R K, VERMA G K, et al. Solvent-Free Sonochemical One-Pot Three-Component Synthesis of 2H-Indazolo[2,1-b]Phthalazine-1,6,11-Triones and 1H-Pyrazolo[1,2-b]Phthalazine-5,10-Diones[J]. Tetrahedron Lett, 2011,52(52):7195-7198.
[73]MULAKAYALA N, PAVAN KUMAR G RAMBABU D, et al. A Greener Synthesis of 1,8-Dioxo-Octahydroxanthene Derivatives under Ultrasound [J]. Tetrahedron Lett,2012,53(51):6923-6926.
[74]ZARE A, MOOSAVI-ZARE A R, MERAJODDIN M, et al. Ionic Liquid Triethylamine-Bonded Sulfonic Acid [[Et3N-SO3H]Cl] as A Novel, Highly Efficient and Homogeneous Catalyst for The Synthesis of B-Acetamido Ketones, 1,8-Dioxo-Octahydroxanthenes and 14-Aryl-14H-Dibenzo[α,j] Xanth-enes[J]. J Mol Liq,2012,167:69-77.
[75]SAFAEI-GHOMI J, GHASEMZADEH M A. Zinc Oxide Nanoparticles, A Highly Efficient and Readily Recyclable Catalyst for the Synthesis of Xanthenes[J]. Chinese Chem Lett,2012:23(11):1225-1229.
[76]ZHANG Fuyi, WANG Yuxin, YANG Fengling, et al. Efficient Solvent-Free Knoevenagel Condensation between β-Diketone and Aldehyde Catalyzed by Silica Sulfuric Acid[J]. Synthetic Commun,2011,41(3):347-356.
[77]MULAKAYALA N, MURTHY P V N S, RAMBABU D, et al. Catalysis by Molecular Iodine:A Rapid Synthesis of 1,8-Dioxo-Octahydroxanthenes and Their Evaluation as Potential Anticancer Agents[J]. Bioorg Med Chem Lett, 2012,22(6):2186-2191.
[78]VERMA G K, RAGHUVANSHI K, VERMA R K, et al. An Efficient One-Pot Solvent-Free Synthesis and Photophysical Properties of 9-Aryl/Alkyl-Octahydroxanthene-1,8-Diones[J]. Tetrahedron,2011,67(20):3698-3704.
[79]Kumar Dhruva, Sandhu J S. Efficient, Solvent-Free, Microwave-Enhanced Condensation of 5,5-Dimethyl-1,3-Cyclohexanedione with Aldehydes and Imines Using Libr as Inexpensive, Mild Catalyst[J]. Synthetic Commun,2010, 40(4):510-517.
[80]LIANG BO, KALIDINDI S, PORCO J A, et al. Multicomponent Reaction Discovery:Three-Component Synthesis of Spirooxindoles[J]. Org Lett,2010, 12(3):572-575.
[81]HINTERMANN L, MASUO R, AND SUZUKI K. Solvent-Controlled Leaving-Group Selectivity in Aromatic Nucleophilic Substitution[J]. Org Lett, 2010,10(21):4859-4862.
[82]BARBERO N, SANMARTIN R, DOMINGUEZ E. A Convenient Approach to the Xanthone Scaffold by An Aqueous Aromatic Substitution of Bromo- And Iodoarenes[J]. Tetrahedron,2009,65(29-30):5729-5732.
[83]GOBBI S, RAMPA A, BISI A, et al. Synthesis and Antitumor Activity of New Derivatives of Xanthen-9-One-4-Acetic Acid[J]. J Med Chem,2002,45(22): 4931-4939.
[84]ZHAO J, LAROCK R C. Synthesis of Xanthones, Thioxanthones, and Acridones by the Coupling of Arynes and Substituted Benzoates[J]. J Org Chem,2007,72 (2):583-588.
[85]OKUMA K, NOJIMA AKIKO, MATSUNAGA N, et al. Reaction of Benzyne with Salicylaldehydes:General Synthesis of Xanthenes, Xanthones, and Xanthols[J]. Org Lett,2009,11(1):169-171.
[86]KISHORE D, RODRIGUES, A E. Liquid Phase Selective Oxidation of Dipheny-lmethane to Benzophenone over Ternary Hydrotalcites with Tert-Butylhydroper-oxide[J]. Catal Commun,2009,10(8):1212-1215.
[87]NOURELDIN N A, ZHAO D Y, LEE D G. Heterogeneous Permanganate Oxida-tions.7. The Oxidation of Aliphatic Side Chains[J]. J Org Chem,1997,62(25): 8767-8772.
[88]KOTANI M, KOIKE T, YAMAGUCHI K, et al. Ruthenium Hydroxide on Magnetite as A Magnetically Separable Heterogeneous Catalyst for Liquid-Phase Oxidation and Reduction[J]. Green Chem,2006,8(8):735-741.
[89]CARUSO A J, LEE J L. A New Reaction of Bisphenol A and Preparation of Polysubstituted 9,9-Dimethylxanthenes[J]. J Org Chem,1997,62(4):1058-1063.
[90]SHELDON R A. Atom Efficiency and Catalysis in Organic Synthesis[J]. Pure Appl Chem,2000,72(7):1233-1246.
[91]JAMISON J M, KRABILL K, HATWALKAR A, et al. Potentiation of The Antiviral Activity of Poly r(A-U) by Xanthene Dyes[J].Cell Biol Int Rep,1990, 14(12):1075-1084.
[92]POUPELIN J P, SAINT-RUF G, FOUSSARD-BLANPIN O, et al. Synthesis and Antiinflammatory Properties of Bis(2-Hydroxy-l-Naphthyl)Methane Derivatives. I. Monosubstituted derivatives [J]. Eur J Med Chem,1978,13(1):67-71.
[93]ION R M, PLANNER A, WIKTOROWICZ K, et al. The Incorporation of Various Porphyrins into Blood Cells Measured via Flow Cytometry, Absorption and Emission Spectroscopy[J]. Acta Biochim Pol,1998,45(3):833-845.
[94]SAINT-RUF G, HIEU H T, POUPELIN J P. The Effect of Dibenzoxanthenes on the Paralyzing Action of Zoxazolamine[J]. Naturwissenschaften,1975,62(12): 584-585.
[95]PEDRO M, CERQUEIRA F, SOUSA M E, et al. Xanthones as Inhibitors of Growth of Human Cancer Cell Lines and Their Effects on the Proliferation of Human Lymphocytes In Vitro[J]. Bioorg Med Chem,2002,10(12):3725-3730.
[96]ZOU Yingshu, HOU Aijun, ZHU Guofu, et al. Cytotoxic Isoprenylated Xanthones from Cudrania Tricuspidata[J]. Bioorg Med Chem,2004,12 (8): 1947-1953.
[97]LIN C N, LIOU S J, LEE T H, et al. Xanthone Derivatives as Potential Anti-Cancer Drugs[J]. J Phm Pharmacol,1996,48(5):539-544.
[98]KUPCHAN S M, STREELMAN D R, SNEDEN A T. Psorospermin, A New Antileukemic Xanthone from Psorospermum febrifugum[J]. J Nat Prod,1980, 43(2):296-301.
[99]WOO S, JUNG J, LEE C, et al. Synthesis of New Xanthone Analogues and Their Biological Activity Test-Cytotoxicity, Topoisomerase Ⅱ Inhibition, and DNA Cross-Linking Study [J]. Bioorg Med Chem Lett,2007,17(5):1163-1166.
[100]TOSA H, IINUMA M, TANAKA T, et al. Inhibitory Activity of Xanthone Derivatives Isolated from Some Guttiferaeous Plants Against DNA Topoisomerases Ⅰ And Ⅱ [J]. Chem Pharm Bull,1997,45(2):418-420.
[101]SITTISOMBUT C, COSTESN, MICHEL S, et al. Synthesis and Cytotoxic Activity of Benzopyranoxanthone Analogues of Benzo[b]acronycine and Psorospermine[J]. Chem Pharm Bull,2001,49(6):675-679.
[102]SITTISOMBUT C, BOUTEFNOUCHET S, VAN-DUFAT H T, et al. Synthesis and Cytotoxic Activity of Benzo[A]Pyrano[3,2-H] and [2,3-i]Xanthone Analogues of Psorospermine, Acronycine, and Benzo[a]acronycine[J]. Chem Pharm Bull,2006,54(8):1113-1118.
[103]BHATTACHARYA A K, RANA K C, MUJAHID M, et al. Synthesis and in Vitro Study of 14-Aryl-14H-Dibenzo[a.j]xanthenes as Cytotoxic Agents [J]. Bioorg Med Chem Lett,2009,19:5590-5593.
[104]STEVENSON P C, VEITCH N C. A 2-Arylbenzofuran from Roots of Cicer Bijugum Associated with Fusarium Wilt Resistance[J]. Phytochemistry,1998, 48(6):947-951.
[105]Aslam S N, Stevenson P C, Kokubun T, et al. Antibacterial and Antifungal Activity of Cicerfuran and Related 2-Arylbenzofurans and Stilbenes[J]. Microbiol Res,2009,164(2):191-195.
[106]MENDONCA PAULETTI P, ARAUJO A R, YOUNG M C M, et al. Nor-Ligna-ns from The Leaves of Styrax Ferrugineus (Styracaceae) with Antibacterial and Antifungal Activity[J]. Phytochemistry,2000,55(6):597-601.
[107]PACHER T, SEGER C, ENGELMEIER D, et al. Antifungal Stilbenoids from Stemona Collinsae[J]. J Nat Prod,2002,65(6):820-827.
[108]MAEDA S, MASUDA H, TOKOROYAMA T. Studies on The Preparation of Bioactive Lignans of Oxidative Coupling Reaction. I. Preparation and Lipid Peroxidation Inhibitory Effect of Benzofuran Lignans Related to Schizotenuins[J].Chem Pharm Bull,1994,42(12):2500-2505.
[109]MIYASE T, SANO M, NAKAI H, et al. Antioxidants from Lespedeza Homoloba. (I)[J]. Phytochemistry,1999,52(2):303-310.
[110]ERASTO P, BOJASE-MOLETA G, MAJINDA R R T. Antimicrobial and Antioxidant Flavonoids from The Root Wood of Bolusanthus Speciosus[J]. Phytochemistry,2004,65(7):875-880.
[111]KAPCHE G D W F, FOZING C D, DONFACK J H, et al. Prenylated Arylbenzofuran Derivatives from Morus Mesozygia with Antioxidant Activity[J]. Phytochemistry,2009,70(2):216-221.
[112]DAI J R, HALLOCK Y F, CARDELLINA J H, et al. HIV-Inhibitory and Cytotoxic Oligostilbenes from The Leaves of Hopea Malibato[J]. J Nat Prod, 1998,61(3),351-353.
[113]PIETERS L, VAN D S, GAO M, et al. Synthesis and Biological Evaluation of Dihydrobenzofuran Lignans and Related Compounds as Potential Antitumor Agents That Inhibit Tubulin Polymerization[J]. J Med Chem,1999,42(26): 5475-5481.
[114]Katsanou E S, Halabalaki M, Aligiannis N, et al. Cytotoxic effects of 2-aryl-benzofuran phytoestrogens on human cancer cells:Modulation by adrenal and gonadal steroids[J]. J Steroid Biochem Mol Biol,2007,104(3-5),228-236.
[115]Ni, G, Zhang, Q J, Zheng Z F, et al.2-Arylbenzofuran derivatives from Morus cathayana[J]. J Nat. Prod.2009,72(5)966-968.
[116]NGUYEN P H, LE T V T, THUONG P T, et al. Cytotoxic and PTP1B Inhibitory Activities from Erythrina Abyssinica[J]. Bioorg Med Chem Lett,2009,19(23): 6745-6749.
[117]DAT N T, JIN X, LEE K, et al. Hypoxia-Inducible Factor-1 Inhibitory Benzo-furans and Chalcone-Derived Diels-Alder Adducts from Morus Species [J]. J Nat Prod,2009,72(1):39-43.
[118]OHYAMA K, TOMONARI M, ICHIBANGASE T, et al. A Toxicoproteomic Study on Cardioprotective Effects of Pre-Administration of Docetaxel in A Mouse Model of Adriamycin-Induced Cardiotoxicity[J]. Biochem Pharmacol, 2010,80(4):540-547.
[119]CAPPS D B, DUNBAR J, KESTEN S R, et al.2-(Aminoalkyl)-5-Nitropyrazolo [3,4,5-Kl]Acridines, A New Class of Anticancer Agents[J]. J Med Chem, 1992,35(26):4770-4778.
[120]HYZY M, BOZKO P, KONOPA J, et al. Antitumour Imidazoacridone C-1311 Induces Cell Death by Mitotic Catastrophe in Human Colon Carcinoma Cells[J]. Biochem Pharmacol,2005,69(5):801-809.
[121]VILCHES-HERRERA M, MIRANDA-SEPULVEDA J, REBOLLEDO-FUEN-TES M, et al. Naphthylisopropylamine and N-benzyl amphetamine Derivatives as Monoamine Oxidase Inhibitors[J]. Bioorg Med Chem,2009,17(6):2452-2460.
[122]LIANG Yonghong, HE Qiuqin, ZENG Zhaosen, et al. Synthesis and Anti-HIV Activity of 2-Naphthyl Substituted DAPY Analogues as Non-nucleoside Reverse Transcriptase Inhibitors[J]. Bioorg Med Chem,2010,18 (13):4601-4605.
[123]JIN Tongshou, LIU Libin, YIN Ying. Clean Synthesis of 14-Alkyl and 14-Aryl-14H-Dibenzo[a,j]xanthenes [J]. Lett Org Chem,2006,3(8),591-596.
[124]MOSMANN T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays [J]. J Immunol Methods, 1983,65(1-2),55-63.
[125]VILLEMIN D, SAUVAGET F. Dry Synthesis under Microwave Irradiation:a Rapid and Efficient Coupling of Naphthols[J]. Synlett,1994,6,435-436.
[2]甄永苏.抗肿瘤药物研究与开发[M].北京：化学工业出版社,2004：39-30.
[3]KROEP J R, GELDERBLOM M. Diflomotecan, Apromisingho Mocamptothecin for Cancer Therapy[J], Expert Opin Investig Drugs,2009,18(1):69-75.
[4]JORDAN M A, WILSON L. Microtubules as A Target for Anticancer Drugs [J]. Nat Rev Cancer.2004,4(4):253-265.
[5]DUMONTET C, JORDAN M A, LEE F F Y, et al. Ixabepilone:Targeting BIII-Tubulin Expression in Taxane-Resistant Malignancies[J]. Mol Cancer Ther, 2009,8(1):17-25.
[6]CIGLER T, VAHDAT L T. Eribulin Mesylate for The Treatment of Breast Cancer[J]. Expert Opin Pharmaco,2010,11(9):1587-1593.
[7]THOMAS BOYLE F, COSTELLO G F. Cancer Therapy:A Move to The Molecular Level[J]. Chem Soc Rev.1998,27(1):251-261.
[8]ZHOU J B, GOH B C, Albert D H, et al. ABT-869, A Promising Multi-Targeted Tyrosine Kinase Inhibitor:from Bench to Bedside[J]. J Hematol Oncol,2009,2: 33.
[9]O'HARE T, SHAKESPEARE W C, ZHU X T, et al. AP24534, A Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits The T315I Mutant and Overcomes Mutation-Based Resistance[J]. Cancer Cell,2009,16(5):401-412.
[10]赵玉娜,邢爱敏.酪氨酸蛋白激酶抑制剂Ruxolitinib[J].药学进展,2010,34(11)：523-524.
[II]XIE H, LIN L P, TONG L J, et al. AST-6, A Novel Irreversible Inhibitor of The Epidermal Growth Factor Receptor 1 and 2, Inhibits Tumor Growth Both In Vitro And In Vivo[J]. Mol Cancer Ther.2009,8(12):C50.
[12]谭芬来,张力,赵琼,等,国家一类新药盐酸埃克替尼的药理与临床评价[J].中国新药杂志,2009,18(18)：1691-1694.
[13]LEBOWITZ PF, PRENDERGAST GC. Non-Ras Targets of Farnesyltransferase Inhibitors:Focus on Rho[J].Oncogene,1998,17(11):1439-1445.]
[14]SEBTI S M, HAMILTON A D. New Approaches to Anticancer Drug Design Based on The Inhibition of Farnesyltransferase. Drug Discov Today,1998,3(1): 26-33.
[15]SEPP-LORENZINO L, MA Z, RANDS E, et al. A Peptidomimetic Inhibitor of Farnesyl:Protein Transferase Blocks The Anchorage-Dependent and Independ-ent Growth of Human Tumor Cell Lines[J]. Cancer Res,1995,55(22):5302-5309.
[16]XIE J J, XU L Y, XIE Y M, et al. Roles of Ezrin in The Growth and Invasiveness of Esophageal Squamous Carcinoma Cells[J]. Int J Cancer.2009,124(11):2549-2558.
[17]INFANTE J R, FECHER L A, NALLAPAREDDY S, et al. Safety and Efficacy Results from The First-In-Human Study of The Oral MEK 1/2 Inhibitor GSK1120212[J]. J Clin Oncol,2010,28(15):2503-2511.
[18]LEE L, NIU H F, RUEGER R, et al. The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of CH4987655 in Healthy Volunteers:Target Suppression Using A Biomarker[J]. Clin Cancer Res,2009, 15(16):7368-7377.
[19]PEROLLET C, HAN ZC, SAVON A C, et al. Platelet Factor 4 Modulates Fibroblast Growth Factor 2 (FGF-2) Activity and Inhibits FGF-2 Dimerization[J]. Blood,1998,91:3289-3299.
[20]MARTIN DC, SANCHEZ-SWEATMAN OH, HO A T, et al. Transgenic TIMP-1 Inhibits Simian Virus 40 T Antigen-Induced Hepatocarcinogenesis by Impairm-ent of Hepatocellular Proliferation and Tumor Angiogenesis[J]. Lab Invest,1999, 79(2):225-234.
[21]MOUSA SA. Mechanisms of Angiogenesis in Vascullar Disorders:Potential Therapeutic Targets[J]. Drugs Fut,1998,23(1):51-60.
[22]SCHLUMBERGER M J, ELISEI R, BASTHOLT L, et al. Phase II Study of Safety and Efficacy of Motesanib in Patients with Progressive or Symptomatic, Advanced or Metastatic Medullary Thyroid Cancer[J]. J Clin Oncol,2009, 27(23):3794-3801.
[23]LEVITZKI A. Signal-Transduction Therapy. A Novel Approach to Disease Man-agement[J]. Eur J Biochem,1994,226(1):1-13.
[24]LEVITZKI A. Protein Tyrosine Kinase Inhibitors as Therapeutic Agents[J]. Top Curr Chem,1998,211(1):1-15.
[25]WHITECHEAD R P, RANKIN C, HOFF P M G, et al. Phase Ⅱ Trial of Romidepsin (NSC-630176) in Previously Treated Colorectal Cancer Patients with Advanced Disease:A Southwest Oncology Group Study(S0336)[J]. Invest New Drugs,2009,27(5):469-475.
[26]FLORES I, BLASCO MA. The Role of Telomeres and Telomerase in Stem Cell Aging[J]. FEBS Lett,2010,584(17):3826-3830.
[27]CHEN W, CHEN SM, YU Y, et al. Telomerase Inhibition Alters Telomere Maintenance Mechanisms in Laryngeal Squamous Carcinoma Cells[J]. J Lary-ngol Otol,2010,124(7):778-783.
[28]FENG J, FUNK W D, WANG S S, et al. The RNA Component of Human Telomerase. Science,1995,269(5228):1236-1241.
[29]SUMI M, TAUCHI T, SASHIDA G, et al. A G-Quadruplex-Interactive Agent, Telomestatin (Sot-095), Induces Telomere Shortening with Apoptosis and Enhance Schemosensitivity in Acute Myeloid Leukemia[J]. Int J Oncol,2004, 24(6):1481-1487.
[30]ZHOU J M, ZHU X F, LU YJ, et al. Senescence and Telomere Shortening Induced by Novel Potent G-Quadruplex Interactive Agents, Quindoline Derivatives, in Human Cancer Cell Lines[J]. Oncogene,2006,25(4):503-511.
[31]TURK D, SZAKACS G. Relevance of Multidrug Resistance in The Age of Targ-eted Therapy [J]. Curr Opin Drug Dis Dev,2009,12(2):246-252.
[32]TEODORI E, DEI S, QUIDU P, et al. Design, Synthesis, and In Vitro Activity of Catamphiphilic Reverters of Multidrug Resistance:Discovery of A Selective, Highly Efficacious Chemosensitizer with Potency in The Nanomolar Range[J]. J Med Chem,1999,42(10):1687-1697.
[33]VOLM M. Multidrug Resistance and Its Reversal[J]. Anticancer Res,1998, 18(4C):2905-2917.
[34]巫凤娟,杨臻峥,孙大柠.抗癌药ABT-263[J].药学进展,2009,33(7)：330-332.
[35]BILLAM M, SOBOLEWSKI M D, DAVIDSON N E. Effects of A Novel DNA Methyltransferase Inhibitor Zebularine on Human Breast Cancer Cells[J]. Breast Cancer Res Treat,2010,120(3):581-592.
[36]SHANGARY S, WANG S. Small-molecule Inhibitors of The MDM2-P53 Protein-Protein Interaction to Reactivate P53 Function:A Novel Approach for Cancer Therapy[J]. Annu Rev Pharmacol Toxicol,2009,49(1):223-241.
[37]XUAN Y, HU X. Naturally-occurring Shikonin Analogues-A Class of Necropto-tic Inducers That Circumvent Cancer Drug Resistance[J]. Cancer Lett.2009, 274(2):233-242.
[38]ASHIMORI N, ZEITLIN B D, ZHANG Z C, et al. TW-37, A Small-Molecule Inhibitor of Bcl-2, Mediates S-Phase Cell Cycle Arrest and Suppresses Head and Neck Tumor Angiogenesis[J]. Mol Cancer Ther,2009,8(4):893-903.
[39]PIERCE J N, STEIN S. Multiple Diversity with Nonindependent Fading[J]. Proceedings of the IRE,1960,48(1):89-104.
[40]FRIEDMAN H, CEGLOWSKI WS. Leukemia Virus-Induced Immuno-suppression Ⅷ. Rapid Depression of In Vitro Leukocyte Migration after Infection of Mice with Friend Leukemia Virus[J]. J Immunol,1971,107(6): 1673-1681.
[41]董倩,姜达.实体瘤诱导分化治疗研究现状[J].肿瘤学杂志,2004,10(6)：443-446.
[42]郑小卫.抗肿瘤药物研究新进展[J].四川生理科学杂志,2007,29(4)：170-173.
[43]MINOTTI G, MENNA P, SALVATORELLI E, et al. Anthracyclines:Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity[J]. Pharmacol Rev.2004,56(2):185-229.
[44]LAUNCHBURY A P, HABBOUBI N. Epirubicin and Doxorubicin:A Comparis-on of Their Characteristics, Therapeutic Activity and Toxicity[J]. Cancer Treat Rev.1993,19(3):197-228.
[45]BONADONNA G, GIANNI L, SANTORO A, et al. Drugs Ten Years Later: Epirubicin[J]. Ann Oncol.1993,4(5):359-369.
[46]TAATJES D J, FENICK D J, KOCH T H. Nuclear Targeting and Nuclear Retention of Anthracycline-Formaldehyde Conjugates Implicates DNA Covalent Bonding in the Cytotoxic Mechanism of Anthracyclines[J]. Chem Res Toxicol, 1999,12(7):588-596.
[47]MORO S, BERETTA G L, DAL BEN D, et al. Interaction Model for Anthracycline Activity Against DNA Topoisomerase Ⅱ[J]. Biochemistry,2004, 43(23):7503-7513.
[48]ANDFIVON W, SAUCIER J M, AUCLAIR C, et al. Enhanced Topoisomerase II-Induced DNA Breaks and Free Radical Production by A New Anthracycline with Potent Antileukemic Activity[J]. Leuk Res,1996,20(2):119-126.
[49]SUN I L, CRANE F L, LOW H, et al. Inhibition of Plasma Membrane NADH Dehydrogenase by Adriamycin and Related Anthracycline Antibiotics [J]. J Bioenerg Biomembr.1984,16(3):209-221.
[50]阴键,郭力芳.中药现代研究与临床应用[M].北京：学苑山版社,1993：435.
[51]胡凯文,侯丽,陈信义,等.大黄酸/大黄素抗多药耐药肿瘤细胞研究[J].中国中医基础药学杂志,1998,4(11)：19-20.
[52]SU H Y, CHERNG S H, CHEN C C, et al. Emodin Inhibits The Mutagenicity and DNA Adducts Induced by 1-Nitropyrene. Mutat Res,1995,329(6):205-212.
[53]ZHANG L, CHANGC J, BACUS SS, et al. Suppressed Transformation and Induced Differentiation of HER-2/neu-overexpressing Breast Cancer Cells by Emodin[J]. Cancer Res,1995,55:3890-3896.
[54]SAFAEI-GHOMI J, GHASEMZADEH M A. Zinc Oxide Nanoparticles, A Highly Efficient and Readily Recyclable Catalyst for the Synthesis of XanthenesfJ]. Chin Chem Lett,2012,23(11):1225-1229.
[55]ZARE A, MOOSAVI-ZARE A R, MERAJODDIN M, et al. Ionic Liquid Triethylamine-Bonded Sulfonic Acid [[Et3N-SO3H]Cl] as A Novel, Highly Efficient and Homogeneous Catalyst for the Synthesis of β-Acetamido Ketones, 1,8-Dioxo-Octahydroxanthenes and 14-Aryl-14H-Dibenzo[a,j]Xanthenes[J]. J Mol Liq,2012,167:69-77.
[56]SHARMA M, MANOHAR S, RAWAT D S. Lewis Acid Catalyzed Synthesis of 1-Aryl-1,2-Dihydronaphtho[1,2-e][1,3]Oxazin-3-Ones under Solvent Free Conditions:A Mechanistic Approach[J]. J Heterocyclic Chem,2012,49(3): 589-595.
[57]GHASSAMIPOUR S, SARDARIAN A R. Facile Catalyzed Preparation of 14-Aryl- or -Alkyl-14-H-Dibenzo[a,j]Xanthenes by Dodecylphosphonic Acid and Dodecylsulfamic Acid:Environmentally Benign Methods[J]. J Heterocyclic Chem,2012,49(3):669-674.
[58]Prasad D, Nath M. PEG-SO3H Catalyzed, Environmentally Benign Synthesis of 14-Aryl-14H-Dibenzo[aj]Xanthenes under Solvent-Free Conditions[J]. Catal Sci Technol,2012,2(1):93-96.
[59]MOHAMMED N N G, PANDHARPATTE M S. Microwave Promoted, Perch-Loric Acid-Catalyzed One-Pot Synthesis of Xanthene Derivatives under Solvent-Free Conditions[J]. Der Pharma Chemica,2011,3(1):65-71.
[60]SOLEIMANI E, KHODAEI M M, KOSHVANDI A T K. The Efficient Synthesis of 14-Alkyl or Aryl 14H-Dibenzo[α,j]Xanthenes Catalyzed by Bismuth(Ⅲ) Chloride under Solvent-Free Conditions [J]. Chinese Chem Lett,2011,22(8): 927-930.
[61]TABATABAEIAN K, KHORSHIDI A, MAMAGHANI M, et al. Facile and Efficient Method for The Synthesis of 14-Substituted-14-H-Dibenzo[α,j] Xanthenes Catalyzed by Ruthenium Chloride Hydrate as A Homogeneous Catalyst[J]. Synthetic Commun,2011,41(10):1427-1434.
[62]WANG Bo, LI Pinhua, ZHANG Yicheng, et al. FeCl3-Catalyzed Condensation of 2-Naphthol and Aldehydes under Solvent-Free Reaction Conditions. An Efficient and Green Alternative for the Synthesis of 14-Aryl(Alkyl)-14H-Dibenzo[α, j]Xanthenes[J]. Chinese J Chem,2010,28(12):2463-2468.
[63]KARIMI-JABERI, Z, KESHAVARZI M. Efficient One-Pot Synthesis of 14-Substituted-14H-Dibenzo[a,j]Xanthenes Using Boric Acid under Solvent-Free Conditions[J]. Chinese Chem Lett,2010,21(5):547-549.
[64]Kumar A, Sharma S, Maurya R A, et al. Diversity Oriented Synthesis of Benzox-anthene and Benzochromene Libraries via One-Pot, Three-Component Reactions and Their Anti-proliferative Activity [J]. J Comb Chem,2010,12(1):20-24.
[65]Kumar R, Nandi G C, Verma R K, et al. A Facile Approach for the Synthesis of 14-Aryl- or Alkyl-14H-Dibenzo[α,j]Xanthenes under Solvent-Free Condition[J]. Tetrahedron Lett,2010,51(2):442-445.
[66]KUMAR C N S S P, SRINIVAS C, SADHU P S, et al. Efficient Synthesis of 14-Substituted-14- H-Dibenzo[α,j]Xanthenes Using Silica Supported Sodium Hydrogen Sulfate or Amberlyst-15 Catalyst[J]. J Heterocyclic Chem,2009, 46(5):997-999.
[67]JHA A, BEAL J. Convenient Synthesis of 12H-Benzo[a]Xanthenes from 2-Tetra-lone[J]. Tetrahedron Lett.2004,45(49):8999-9001.
[68]OLYAEI A, GESMATI F, SADEGHPOUR M, et al. Synthesis of Novel Anil-Like Compounds from Heteroaryl Amines, Naphthols, and Triethylorthoforma-te Under Solvent-Free Conditions[J]. Synth Commun,2012,42(11):1650- 1660.
[69]ZHANG X, LIU Q, SON A, et al. Photophysical Properties of Dibenzofluoresce-in and The Presence of its Tautomers or Prototropic Forms in Organic Solvents[J]. Photochem Photobiol Sci,2008,7(3):299-302.
[70]Banihashemi A, Rahmatpour A. First Synthesis of 1,1,4,4-Tetrakis(2-hydroxyp henyl)butane Type Compounds from Condensation of p-Substituted Phenol Derivatives with 2,5-Dimethoxytetrahydrofuran in Trifluoroacetic Acid[J]. J Chem Res Synop,1999,6:390-391.
[71]史达清,庄启亚,陈景,等.水溶剂中芳醛与5,5-二甲基-1,3-坏己二酮的反应[J].有机化学,2003,23(7)：694-696.
[72]SHUKLA G, VERMA R K, VERMA G K, et al. Solvent-Free Sonochemical One-Pot Three-Component Synthesis of 2H-Indazolo[2,1-b]Phthalazine-1,6,11-Triones and 1H-Pyrazolo[1,2-b]Phthalazine-5,10-Diones[J]. Tetrahedron Lett, 2011,52(52):7195-7198.
[73]MULAKAYALA N, PAVAN KUMAR G RAMBABU D, et al. A Greener Synthesis of 1,8-Dioxo-Octahydroxanthene Derivatives under Ultrasound [J]. Tetrahedron Lett,2012,53(51):6923-6926.
[74]ZARE A, MOOSAVI-ZARE A R, MERAJODDIN M, et al. Ionic Liquid Triethylamine-Bonded Sulfonic Acid [[Et3N-SO3H]Cl] as A Novel, Highly Efficient and Homogeneous Catalyst for The Synthesis of B-Acetamido Ketones, 1,8-Dioxo-Octahydroxanthenes and 14-Aryl-14H-Dibenzo[α,j] Xanth-enes[J]. J Mol Liq,2012,167:69-77.
[75]SAFAEI-GHOMI J, GHASEMZADEH M A. Zinc Oxide Nanoparticles, A Highly Efficient and Readily Recyclable Catalyst for the Synthesis of Xanthenes[J]. Chinese Chem Lett,2012:23(11):1225-1229.
[76]ZHANG Fuyi, WANG Yuxin, YANG Fengling, et al. Efficient Solvent-Free Knoevenagel Condensation between β-Diketone and Aldehyde Catalyzed by Silica Sulfuric Acid[J]. Synthetic Commun,2011,41(3):347-356.
[77]MULAKAYALA N, MURTHY P V N S, RAMBABU D, et al. Catalysis by Molecular Iodine:A Rapid Synthesis of 1,8-Dioxo-Octahydroxanthenes and Their Evaluation as Potential Anticancer Agents[J]. Bioorg Med Chem Lett, 2012,22(6):2186-2191.
[78]VERMA G K, RAGHUVANSHI K, VERMA R K, et al. An Efficient One-Pot Solvent-Free Synthesis and Photophysical Properties of 9-Aryl/Alkyl-Octahydroxanthene-1,8-Diones[J]. Tetrahedron,2011,67(20):3698-3704.
[79]Kumar Dhruva, Sandhu J S. Efficient, Solvent-Free, Microwave-Enhanced Condensation of 5,5-Dimethyl-1,3-Cyclohexanedione with Aldehydes and Imines Using Libr as Inexpensive, Mild Catalyst[J]. Synthetic Commun,2010, 40(4):510-517.
[80]LIANG BO, KALIDINDI S, PORCO J A, et al. Multicomponent Reaction Discovery:Three-Component Synthesis of Spirooxindoles[J]. Org Lett,2010, 12(3):572-575.
[81]HINTERMANN L, MASUO R, AND SUZUKI K. Solvent-Controlled Leaving-Group Selectivity in Aromatic Nucleophilic Substitution[J]. Org Lett, 2010,10(21):4859-4862.
[82]BARBERO N, SANMARTIN R, DOMINGUEZ E. A Convenient Approach to the Xanthone Scaffold by An Aqueous Aromatic Substitution of Bromo- And Iodoarenes[J]. Tetrahedron,2009,65(29-30):5729-5732.
[83]GOBBI S, RAMPA A, BISI A, et al. Synthesis and Antitumor Activity of New Derivatives of Xanthen-9-One-4-Acetic Acid[J]. J Med Chem,2002,45(22): 4931-4939.
[84]ZHAO J, LAROCK R C. Synthesis of Xanthones, Thioxanthones, and Acridones by the Coupling of Arynes and Substituted Benzoates[J]. J Org Chem,2007,72 (2):583-588.
[85]OKUMA K, NOJIMA AKIKO, MATSUNAGA N, et al. Reaction of Benzyne with Salicylaldehydes:General Synthesis of Xanthenes, Xanthones, and Xanthols[J]. Org Lett,2009,11(1):169-171.
[86]KISHORE D, RODRIGUES, A E. Liquid Phase Selective Oxidation of Dipheny-lmethane to Benzophenone over Ternary Hydrotalcites with Tert-Butylhydroper-oxide[J]. Catal Commun,2009,10(8):1212-1215.
[87]NOURELDIN N A, ZHAO D Y, LEE D G. Heterogeneous Permanganate Oxida-tions.7. The Oxidation of Aliphatic Side Chains[J]. J Org Chem,1997,62(25): 8767-8772.
[88]KOTANI M, KOIKE T, YAMAGUCHI K, et al. Ruthenium Hydroxide on Magnetite as A Magnetically Separable Heterogeneous Catalyst for Liquid-Phase Oxidation and Reduction[J]. Green Chem,2006,8(8):735-741.
[89]CARUSO A J, LEE J L. A New Reaction of Bisphenol A and Preparation of Polysubstituted 9,9-Dimethylxanthenes[J]. J Org Chem,1997,62(4):1058-1063.
[90]SHELDON R A. Atom Efficiency and Catalysis in Organic Synthesis[J]. Pure Appl Chem,2000,72(7):1233-1246.
[91]JAMISON J M, KRABILL K, HATWALKAR A, et al. Potentiation of The Antiviral Activity of Poly r(A-U) by Xanthene Dyes[J].Cell Biol Int Rep,1990, 14(12):1075-1084.
[92]POUPELIN J P, SAINT-RUF G, FOUSSARD-BLANPIN O, et al. Synthesis and Antiinflammatory Properties of Bis(2-Hydroxy-l-Naphthyl)Methane Derivatives. I. Monosubstituted derivatives [J]. Eur J Med Chem,1978,13(1):67-71.
[93]ION R M, PLANNER A, WIKTOROWICZ K, et al. The Incorporation of Various Porphyrins into Blood Cells Measured via Flow Cytometry, Absorption and Emission Spectroscopy[J]. Acta Biochim Pol,1998,45(3):833-845.
[94]SAINT-RUF G, HIEU H T, POUPELIN J P. The Effect of Dibenzoxanthenes on the Paralyzing Action of Zoxazolamine[J]. Naturwissenschaften,1975,62(12): 584-585.
[95]PEDRO M, CERQUEIRA F, SOUSA M E, et al. Xanthones as Inhibitors of Growth of Human Cancer Cell Lines and Their Effects on the Proliferation of Human Lymphocytes In Vitro[J]. Bioorg Med Chem,2002,10(12):3725-3730.
[96]ZOU Yingshu, HOU Aijun, ZHU Guofu, et al. Cytotoxic Isoprenylated Xanthones from Cudrania Tricuspidata[J]. Bioorg Med Chem,2004,12 (8): 1947-1953.
[97]LIN C N, LIOU S J, LEE T H, et al. Xanthone Derivatives as Potential Anti-Cancer Drugs[J]. J Phm Pharmacol,1996,48(5):539-544.
[98]KUPCHAN S M, STREELMAN D R, SNEDEN A T. Psorospermin, A New Antileukemic Xanthone from Psorospermum febrifugum[J]. J Nat Prod,1980, 43(2):296-301.
[99]WOO S, JUNG J, LEE C, et al. Synthesis of New Xanthone Analogues and Their Biological Activity Test-Cytotoxicity, Topoisomerase Ⅱ Inhibition, and DNA Cross-Linking Study [J]. Bioorg Med Chem Lett,2007,17(5):1163-1166.
[100]TOSA H, IINUMA M, TANAKA T, et al. Inhibitory Activity of Xanthone Derivatives Isolated from Some Guttiferaeous Plants Against DNA Topoisomerases Ⅰ And Ⅱ [J]. Chem Pharm Bull,1997,45(2):418-420.
[101]SITTISOMBUT C, COSTESN, MICHEL S, et al. Synthesis and Cytotoxic Activity of Benzopyranoxanthone Analogues of Benzo[b]acronycine and Psorospermine[J]. Chem Pharm Bull,2001,49(6):675-679.
[102]SITTISOMBUT C, BOUTEFNOUCHET S, VAN-DUFAT H T, et al. Synthesis and Cytotoxic Activity of Benzo[A]Pyrano[3,2-H] and [2,3-i]Xanthone Analogues of Psorospermine, Acronycine, and Benzo[a]acronycine[J]. Chem Pharm Bull,2006,54(8):1113-1118.
[103]BHATTACHARYA A K, RANA K C, MUJAHID M, et al. Synthesis and in Vitro Study of 14-Aryl-14H-Dibenzo[a.j]xanthenes as Cytotoxic Agents [J]. Bioorg Med Chem Lett,2009,19:5590-5593.
[104]STEVENSON P C, VEITCH N C. A 2-Arylbenzofuran from Roots of Cicer Bijugum Associated with Fusarium Wilt Resistance[J]. Phytochemistry,1998, 48(6):947-951.
[105]Aslam S N, Stevenson P C, Kokubun T, et al. Antibacterial and Antifungal Activity of Cicerfuran and Related 2-Arylbenzofurans and Stilbenes[J]. Microbiol Res,2009,164(2):191-195.
[106]MENDONCA PAULETTI P, ARAUJO A R, YOUNG M C M, et al. Nor-Ligna-ns from The Leaves of Styrax Ferrugineus (Styracaceae) with Antibacterial and Antifungal Activity[J]. Phytochemistry,2000,55(6):597-601.
[107]PACHER T, SEGER C, ENGELMEIER D, et al. Antifungal Stilbenoids from Stemona Collinsae[J]. J Nat Prod,2002,65(6):820-827.
[108]MAEDA S, MASUDA H, TOKOROYAMA T. Studies on The Preparation of Bioactive Lignans of Oxidative Coupling Reaction. I. Preparation and Lipid Peroxidation Inhibitory Effect of Benzofuran Lignans Related to Schizotenuins[J].Chem Pharm Bull,1994,42(12):2500-2505.
[109]MIYASE T, SANO M, NAKAI H, et al. Antioxidants from Lespedeza Homoloba. (I)[J]. Phytochemistry,1999,52(2):303-310.
[110]ERASTO P, BOJASE-MOLETA G, MAJINDA R R T. Antimicrobial and Antioxidant Flavonoids from The Root Wood of Bolusanthus Speciosus[J]. Phytochemistry,2004,65(7):875-880.
[111]KAPCHE G D W F, FOZING C D, DONFACK J H, et al. Prenylated Arylbenzofuran Derivatives from Morus Mesozygia with Antioxidant Activity[J]. Phytochemistry,2009,70(2):216-221.
[112]DAI J R, HALLOCK Y F, CARDELLINA J H, et al. HIV-Inhibitory and Cytotoxic Oligostilbenes from The Leaves of Hopea Malibato[J]. J Nat Prod, 1998,61(3),351-353.
[113]PIETERS L, VAN D S, GAO M, et al. Synthesis and Biological Evaluation of Dihydrobenzofuran Lignans and Related Compounds as Potential Antitumor Agents That Inhibit Tubulin Polymerization[J]. J Med Chem,1999,42(26): 5475-5481.
[114]Katsanou E S, Halabalaki M, Aligiannis N, et al. Cytotoxic effects of 2-aryl-benzofuran phytoestrogens on human cancer cells:Modulation by adrenal and gonadal steroids[J]. J Steroid Biochem Mol Biol,2007,104(3-5),228-236.
[115]Ni, G, Zhang, Q J, Zheng Z F, et al.2-Arylbenzofuran derivatives from Morus cathayana[J]. J Nat. Prod.2009,72(5)966-968.
[116]NGUYEN P H, LE T V T, THUONG P T, et al. Cytotoxic and PTP1B Inhibitory Activities from Erythrina Abyssinica[J]. Bioorg Med Chem Lett,2009,19(23): 6745-6749.
[117]DAT N T, JIN X, LEE K, et al. Hypoxia-Inducible Factor-1 Inhibitory Benzo-furans and Chalcone-Derived Diels-Alder Adducts from Morus Species [J]. J Nat Prod,2009,72(1):39-43.
[118]OHYAMA K, TOMONARI M, ICHIBANGASE T, et al. A Toxicoproteomic Study on Cardioprotective Effects of Pre-Administration of Docetaxel in A Mouse Model of Adriamycin-Induced Cardiotoxicity[J]. Biochem Pharmacol, 2010,80(4):540-547.
[119]CAPPS D B, DUNBAR J, KESTEN S R, et al.2-(Aminoalkyl)-5-Nitropyrazolo [3,4,5-Kl]Acridines, A New Class of Anticancer Agents[J]. J Med Chem, 1992,35(26):4770-4778.
[120]HYZY M, BOZKO P, KONOPA J, et al. Antitumour Imidazoacridone C-1311 Induces Cell Death by Mitotic Catastrophe in Human Colon Carcinoma Cells[J]. Biochem Pharmacol,2005,69(5):801-809.
[121]VILCHES-HERRERA M, MIRANDA-SEPULVEDA J, REBOLLEDO-FUEN-TES M, et al. Naphthylisopropylamine and N-benzyl amphetamine Derivatives as Monoamine Oxidase Inhibitors[J]. Bioorg Med Chem,2009,17(6):2452-2460.
[122]LIANG Yonghong, HE Qiuqin, ZENG Zhaosen, et al. Synthesis and Anti-HIV Activity of 2-Naphthyl Substituted DAPY Analogues as Non-nucleoside Reverse Transcriptase Inhibitors[J]. Bioorg Med Chem,2010,18 (13):4601-4605.
[123]JIN Tongshou, LIU Libin, YIN Ying. Clean Synthesis of 14-Alkyl and 14-Aryl-14H-Dibenzo[a,j]xanthenes [J]. Lett Org Chem,2006,3(8),591-596.
[124]MOSMANN T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays [J]. J Immunol Methods, 1983,65(1-2),55-63.
[125]VILLEMIN D, SAUVAGET F. Dry Synthesis under Microwave Irradiation:a Rapid and Efficient Coupling of Naphthols[J]. Synlett,1994,6,435-436.