title: Synthesis, structure-activity relationship and biological evaluation of anticancer activity for novel N-substituted sophoridinic acid derivatives.
abstract: Sophoridine (1), a natural anticancer drug, has been used in China for decades. A series of novel N-substituted sophoridinic acid derivatives were synthesized and evaluated for their cytotoxicity with 1 as the lead. The structure-activity relationship indicated that introduction of an aliphatic acyl on the nitrogen atom might significantly enhance the anticancer activity. Among the compounds, 6b bearing bromoacetyl side-chain afforded a potential effect against four human tumor cell lines (liver, colon, breast, and lung). The mechanism of action of 6b is to inhibit the activity of DNA topoisomerase I, followed by the S-phase arrest and then cause apoptotic cell death, similar to that of its parent 1. We consider 6b promising for further anticancer investigation.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Wu-Li
authors.initials: WL
authors.lastname: Zhao
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Kai-Huan
authors.initials: KH
authors.lastname: Ren
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Du
authors.forename: Yang-Biao
authors.initials: YB
authors.lastname: Li
authors.forename: Yan-Xiang
authors.initials: YX
authors.lastname: Wang
authors.forename: Chong-Wen
authors.initials: CW
authors.lastname: Bi
authors.forename: Rong-Guang
authors.initials: RG
authors.lastname: Shao
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011807:Quinolizines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D011807:Quinolizines; D004264:DNA Topoisomerases, Type I