SYNTHESIS AND IN VITRO ANTITUMOR ACTIVITY OF 9-HYDROXYELLIPTICINE DERIVATIVES WITH GLUCOSE CONJUGATION VIA TRIAZOLYLMETHYL SUCCINATE LINKER

摘要

Three types of novel 9-hydroxyellipticine derivatives 7a-c with glucose conjugation, linked by a triazolylmethyl succinic ester bond, were synthesized, and their cytotoxicity against HeLa S-3 and 293T cells was evaluated together with ellipticine (1) and 9-hydroxyellipticine (3). These new compounds 7a-c exhibited potent antitumor activity against HeLa S-3 and 293T, and water solubility of 7a was greatly higher than those of 1 and 3. The effects of an -OCH2CH2- spacer and the amino sugar moiety on the antitumor activity were examined using 7b,c. Furthermore, one of these glucose-conjugates 7a was applied to hydrolysis, catalyzed by carboxyesterase, leading to the formation of 3 under physiological conditions.