Synthesis and biological evaluation of new homocamptothecin analogs.
In order to increase the stability of E-ring of homocamptothecins, the electron-withdrawing group -OH or -OAc was induced to α position of ring-E lactone. Ten new homocamptothecin analogs were synthesized. Most compounds showed potent in vitro anticancer activity and potent Topo I inhibition, which was equal or superior to that of CPT, SN-38 and 10-HCPT. The stability studies of this series also displayed significant improvement of the stability.
Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, 3663 North Zhongshan Road, East China Normal University, Shanghai 200062, China.
Yu
Y
Luo
Shanbao
S
Yu
Linjiang
L
Tong
Qingqing
Q
Huang
Wei
W
Lu
Yi
Y
Chen
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; C120029:homocamptothecin; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin