title: Synthesis and evaluation of 9-benzylideneamino derivatives of homocamptothecin as potent inhibitors of DNA topoisomerase I.
abstract: 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.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yao
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.forename: Lingjian
authors.initials: L
authors.lastname: Zhu
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Liu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Che
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.forename: Chuan
authors.initials: C
authors.lastname: Luo
authors.forename: Yulan
authors.initials: Y
authors.lastname: Xu
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D004247:DNA; C120029:homocamptothecin; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin