title: Synthesis of 9-(heteroarylmethylidene)amino derivatives of homocamptothecin with biological activities.
abstract: Six 9-(heteroarylmethylidene)amino derivatives, 2a-2f, of homocamptothecin were synthesized for the first time by total synthesis in 22 steps and biologically evaluated as inhibitors of topoisomerase I. Moreover, the antitumor activities of 2a-2f against three human tumor cell lines, i.e., A-549, MDA-MB-435, and HCT-116, were determined and the results showed that compound 2c was the most active homocamptothecin derivative against the A-549 (IC(50) =0.046 μM) and HTC-116 tumor cells (IC(50) =3.67 μM), with a ca. 50 times higher activity than the reference drug topotecan (TPT) against the lung cancer cell line A-549.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR 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: Wenfeng
authors.initials: W
authors.lastname: Liu
authors.forename: Lingjian
authors.initials: L
authors.lastname: Zhu
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Pengfei
authors.initials: P
authors.lastname: Cheng
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zhuang
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
mesh_terms: 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; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; C120029:homocamptothecin; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin