title: Synthesis and biological evaluation of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position as potential antitumor agents.
abstract: A series of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at the C2-position were synthesized and evaluated for their antiproliferative activities against A549, MCF-7, HeLa, HT29 and HCT-116 cell lines. Most of the synthesized compounds exhibited broad spectrum antitproliferative activity against five cell lines, of which 5c was the most potent against HT29 cell line with an IC50 value of 5.53 μM, inducing a G2/M phase arrest in HT29 cells. Treatment of HT29 cells with 5c resulted in BubR1 phosphorylation and an increase of mitotic index in a time-dependent manner. Furthermore, 5c promoted tubulin polymerization in vitro. These results demonstrate that quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position may be potentially novel antitumor agents targeting tubulin to activate the spindle assembly checkpoint.
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Ding
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Man
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Mao
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing, 100048, PR China. Electronic address: slcao@cnu.edu.cn.
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Cao
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Cui-Huan
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Chao-Rui
authors.initials: CR
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Zhong-Feng
authors.initials: ZF
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Liao
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing, 100048, PR China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing, 100048, PR China. Electronic address: xingzhi_xu@mail.cnu.edu.cn.
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C000611423:(4-oxo-3,4-dihydroquinazolin-2-yl)methyl 4-methoxybenzylcarbamodithioate; D000970:Antineoplastic Agents; D052999:Quinazolinones; D013859:Thiocarbamates
keywords: Antiproliferative activity; Dithiocarbamate; G2/M arrest; Quinazolin-4(3H)-one; Spindle assembly checkpoint; Synthesis