title: Discovery of 7-Methyl-10-Hydroxyhomocamptothecins with 1,2,3-Triazole Moiety as Potent Topoisomerase I Inhibitors.
abstract: Homocamptothecin is emerging as an important topoisomerase I inhibitor originating in natural product camptothecin. We report the modifications and SAR of homocamptothecin on position C10 to develop potent topoisomerase I inhibitors for anticancer drug discovery. Based on click chemistry, twenty-one 1,2,3-triazole-substituted homocamptothecin derivatives were readily synthesized in two steps. For A549, cycloalkyl- and alkyl-substituted compounds 6j, 6l, and 6o revealed highly antiproliferative inhibitory activities with IC50 value of 30, 30, and 50 nm, respectively. In addition, cyclopropyl 6j exhibited greater Topo I inhibitory activity than 20(S)-Camptothecin, which indicated suitability for further drug development.
authors.affiliation: School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750004, China.|School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Xiguo
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.|School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, 201418, China.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.|Wuxi App Tec Co., Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai, 200131, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Chuanquan
authors.initials: C
authors.lastname: Sheng
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Fang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Min
authors.affiliation: Department of Radiation Oncology, Shanghai Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
authors.forename: Huojun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.affiliation: School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750004, China.|School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
mesh_terms: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry
chemical_list: D059004:Topoisomerase I Inhibitors; D014230:Triazoles; D002166:Camptothecin
keywords: 1,2,3-triazole; click chemistry; homocamptothecin; topoisomerase I