title: Elaboration of thorough simplified vinca alkaloids as antimitotic agents based on pharmacophore similarity.
abstract: Thorough simplification of vinca alkaloids based on pharmacophore similarity has been conducted. A concise process for the syntheses of target compounds was successfully developed with yields from poor to excellent (19-98%). Cell growth inhibitory activities of these synthesized compounds were evaluated in five cancer cell lines including MCF-7, MDA-MB-231, HepG2, HepG2/ADM and K562. Almost all compounds exhibited moderate antitumor activity with optimal IC50 value of 0.89 ± 0.07 μM in MCF-7 cells. Investigation of structure-activity relationship (SAR) indicates that electron-withdraw substituents on the ring contribute to the enhancement of the antitumor activities. The simplified vinca alkaloids are confirmed as antimitotic agents, which inhibit the polymerization of tubulin just like vinblastine.
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Lijuan
authors.initials: L
authors.lastname: Deng
authors.forename: Minfeng
authors.initials: M
authors.lastname: Chen
authors.forename: Xuzhi
authors.initials: X
authors.lastname: Xiao
authors.forename: Shengwei
authors.initials: S
authors.lastname: Xiao
authors.forename: Cuiping
authors.initials: C
authors.lastname: Guo
authors.forename: Gaokeng
authors.initials: G
authors.lastname: Xiao
authors.forename: Liangliang
authors.initials: L
authors.lastname: Bai
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.forename: Heru
authors.initials: H
authors.lastname: Chen
mesh_terms: D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014748:Vinca Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D050256:Antimitotic Agents; D014748:Vinca Alkaloids
keywords: Anticancer; Antimitotic agent; Pharmacophore similarity; Vinca alkaloid