1422376-70-2Relevant academic research and scientific papers
Novel antitumor indolizino[6,7-b]indoles with multiple modes of action: DNA cross-linking and topoisomerase i and II inhibition
Chaniyara, Ravi,Tala, Satishkumar,Chen, Chi-Wei,Zang, Xiuguo,Kakadiya, Rajesh,Lin, Li-Fang,Chen, Ching-Huang,Chien, Shin-I,Chou, Ting-Chao,Tsai, Tung-Hu,Lee, Te-Chang,Shah, Anamik,Su, Tsann-Long
, p. 1544 - 1563 (2013/04/10)
A series of bis(hydroxymethyl)indolizino[6,7-b]indoles and their bis(alkylcarbamates) were synthesized for antitumor studies. These agents were designed as hybrid molecules of β-carboline (topoisomerase inhibition moiety) and bis(hydroxymethyl)pyrrole (DNA cross-linking moiety). The preliminary antitumor studies indicated that these agents exhibited significant cytotoxicity against a variety of human tumor cells in vitro. Treatment of human breast carcinoma MX-1 xenograft-bearing nude mice with compounds 18b and 28c achieved more than 99% tumor remission. We also observed that 18a displayed potent therapeutic efficacy against human lung adenocarcinoma A549 and colon cancer HT-29 xenografts. These results revealed that compound 18a was more potent than irinotecan against HT-29 cells and was as potent as irinotecan against A549 cells in xenograft models. Furthermore, we demonstrated that these derivatives possess multiple modes of action, such as induction of DNA cross-linking, inhibition of topoisomerase I and II, and cell-cycle arrest at the S-phase.
