Synthesis and evaluation of 9-benzylideneamino derivatives of homocamptothecin as potent inhibitors of DNA topoisomerase I.
A series of novel 9-benzylideneamino derivatives of homocamptothecin were synthesized via Friedlaender cyclization from our obtained intermediate 5. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, LOVO and MDA-MB-435). Most of these derivatives possessed potent growth inhibitory effect on all the tested cell lines and four compounds (6d, 6f, 6i, 6k) showed higher inhibitory activities with the IC50 values of 2.3 nM-9.8 nM against breast cancer cell than topotecan. As compared to CPT, compound 6f revealed higher topoisomerase I inhibitory activity.
Guo
Wei
W
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
Miao
Zhenyuan
Z
Sheng
Chunquan
C
Yao
Jianzhong
J
Feng
Hao
H
Zhang
Wannian
W
Zhu
Lingjian
L
Liu
Wenfeng
W
Cheng
Pengfei
P
Zhang
Jing
J
Che
Xiaoying
X
Wang
Wenya
W
Luo
Chuan
C
Xu
Yulan
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000737:chemistry*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D004247:DNA; C120029:homocamptothecin; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin