Homocamptothecin, an E-ring-modified camptothecin analogue, generates new topoisomerase I-mediated DNA breaks.

摘要: Homocamptothecin (hCPT) contains a seven-membered β-hydroxylactone in place of the conventional six-membered α-hydroxylactone ring found camptothecin and its tumor active analogues, including topotecan irinotecan. The homologation lactone E-ring reinforces stability lactone, thus reducing considerably conversion into carboxylate form which is inactive. We have recently shown that hCPT much more than parent compound against variety cells vitro xenograft models, suggesting highly reactive not essential for topoisomerase I-mediated anticancer activity [Lesueur-Ginot et al. (1999) Cancer Res. 59, 2939−2943]. In present study, we provide further evidence has superior I inhibition capacities to CPT. particular, show replacement with homologous changes sequence-specificity drug-induced DNA cleavage by I...