Substituted benzo[i]phenanthridines as mammalian topoisomerase-targeting agents
作者： Darshan Makhey , Dajie Li , Baoping Zhao , Sai-Peng Sim , Tsai-Kun Li
DOI: 10.1016/S0968-0896(03)00053-1
关键词:
摘要: Several benzo[c]phenanthridine and protoberberine alkaloids, such as nitidine berberrubine, are known to induce DNA cleavage in the presence of either topoisomerase I or II. Structure–activity studies performed on various analogues related alkaloids have provided insights into structural features that influence this topoisomerase-targeting activity. Modifications within A-ring can significantly alter their ability enhance cleavable complex formation occurs between topoisomerases. Select benzo[i]phenanthridines were synthesized potential bioisosteres its analogues. In present study, 2,3-methylenedioxy-8,9-dimethoxybenzo[i]phenanthridine, 2,3-methylenedioxy-8,9-dimethoxy-5-methylbenzo[i]phenanthridine, 2,3,8,9-tetramethoxybenzo[i]phenanthridine 5-methyl-2,3,8,9-tetramethoxybenzo[i]phenanthridine synthesized. These benzo[i]phenanthridine derivatives evaluated for topoisomerases well cytotoxicity against human lymphoblastoma cell line, RPMI8402. 2,3-Methylenedioxy-8,9-dimethoxybenzo[i]phenanthridine (4a) 5-methyl derivative (4b) active I-targeting agents. contrast nitidine, substituent case 4b is not associated with enhanced Consistent previous structure–activity 2,3,8,9-teramethoxybenzo[i]phenanthridine, 5a, derivative,5b, inactive extended an evaluation relative pharmacological activities 2,8,9-trimethoxybenzo[i]phenanthridine, 3,8,9-trimethoxybenzo[i]phenanthridine, 2,3-methylenedioxy-8,9-methylenedioxybenzo[i]phenanthridine.
elsevier.com
sci-hub.se 参考文章(44)
Toshiwo Andoh, Kosuke Okada, Drug resistance mechanisms of topoisomerase I drugs. Advances in pharmacology (San Diego). ,vol. 29, pp. 93- 103 ,(1994) , 10.1016/S1054-3589(08)61133-3
B D Halligan, K A Edwards, L F Liu, Purification and characterization of a type II DNA topoisomerase from bovine calf thymus. Journal of Biological Chemistry. ,vol. 260, pp. 2475- 2482 ,(1985) , 10.1016/S0021-9258(18)89578-3
N. Fujii, Y. Yamashita, Y. Saitoh, H. Nakano, Induction of mammalian DNA topoisomerase I-mediated DNA cleavage and DNA winding by bulgarein Journal of Biological Chemistry. ,vol. 268, pp. 13160- 13165 ,(1993) , 10.1016/S0021-9258(19)38632-6
L F Liu, T C Rowe, L Yang, K M Tewey, G L Chen, Cleavage of DNA by mammalian DNA topoisomerase II. Journal of Biological Chemistry. ,vol. 258, pp. 15365- 15370 ,(1983) , 10.1016/S0021-9258(17)43815-4
Y. Oikawa, O. Yonemitsu, Cyclization of β-ketosulfoxide—III Tetrahedron. ,vol. 30, pp. 2653- 2660 ,(1974) , 10.1016/S0040-4020(01)97425-3
François Denizot, Rita Lang, Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. Journal of Immunological Methods. ,vol. 89, pp. 271- 277 ,(1986) , 10.1016/0022-1759(86)90368-6
Darshan Makhey, Chiang Yu, Barbara Gatto, Edmond J. LaVoie, Marilyn M. Sanders, Hong Yan Wu, Leroy-Fong Liu, Identification of Topoisomerase I as the Cytotoxic Target of the Protoberberine Alkaloid Coralyne Cancer Research. ,vol. 56, pp. 2795- 2800 ,(1996)
Mark Cushman, Prem Mohan, Synthesis and antitumor activity of structural analogues of the anticancer benzophenanthridine alkaloid fagaronine chloride. Journal of Medicinal Chemistry. ,vol. 28, pp. 1031- 1036 ,(1985) , 10.1021/JM00146A010
Jung Sun Kim, Barbara Gatto, Chiang Yu, Angela Liu, Leroy F. Liu, Edmond J. LaVoie, Substituted 2,5'-Bi-1H-benzimidazoles: topoisomerase I inhibition and cytotoxicity. Journal of Medicinal Chemistry. ,vol. 39, pp. 992- 998 ,(1996) , 10.1021/JM950412W
Robert K. Y. Zee-Cheng, C. C. Cheng, Tetramethoxydibenzoquinolizinium salts. Preparation and antileukemic activity of some positional and structural isomers of coralyne. Journal of Medicinal Chemistry. ,vol. 19, pp. 882- 886 ,(1976) , 10.1021/JM00229A005