Synthesis of camptothecin 20(S)-norcantharidine esters and preliminary evaluation of their biological activity in vivo
ZHAO Chang-kuo
WANG Xian-heng
YANG Fu-hong
LI Chan
YUAN Zhi
BAO Yu-jiao
CAO Ying
Abstract：Objective: To improve the anticancer bioactivity of camptothecin, nine camptothecin 20-ester derivatives were designed and synthesized. Methods: Starting from maleic anhydride and furan, [4+2]cyclization addition reaction was conducted to obtain 5-ene-norcantharidin 1, followed by alcololysis to give the corresponding side chain 4a-i, which was then coupled with camptothecin in the condition of EDCI and DMAP to afford camptothecin 20-ester derivatives 7a-i. Inhibition activity against four kinds of tumor cell lines was investigated with CCK-8 method. Results: Compared to the two positive controls, cantharidin and camptothecin, all of the nine target compounds showed comparable inhibition against BGC803 and SW480, and compounds 7b, 7d, 7f and 7g exhibited potent inhibition against HepG2 or PANC-1. Conclusion: The direct coupling products of camptothecin with cantharidin keep the antitumor properties of camptothecin, but weaken the anti-hepatocarcinoma activity of cantharidin. This finding may provide reference for further drug design.
Keywords：camptothecincamptothecin 20(S)-norcantharidin esterCCK-8 methodantitumor activity
Publication Date：2018-01-01
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：9( 960-968 )