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Design, synthesis and pharmacological evaluation of new 2-oxo-quinoline derivatives containing ?-aminophosphonates as potential antitumor agents.

ABSTRACT: A series of novel 2-oxo-quinoline derivatives containing ?-aminophosphonates were designed and synthesized as antitumor agents. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay results demonstrated that some compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3 and NCI-H460 tumor cell lines, and most compounds showed much lower cytotoxicity against HL-7702 normal cells than 5-FU and cisplatin. The action mechanism of representative compound 5b was investigated by fluorescence staining assay, flow cytometric analysis and western blot (WB) assay, which indicated that this compound induced apoptosis and G₂/M phase arrest accompanied by an increase in the production of intracellular Ca²⁺ and reactive oxygen species (ROS) and affecting associated enzymes and genes.

SUBMITTER: Yu YC

PROVIDER: S-EPMC6072518 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Design, synthesis and pharmacological evaluation of new 2-oxo-quinoline derivatives containing α-aminophosphonates as potential antitumor agents.

Yu Yan-Cheng YC Kuang Wen-Bin WB Huang Ri-Zhen RZ Fang Yi-Lin YL Zhang Ye Y Chen Zhen-Feng ZF Ma Xian-Li XL

MedChemComm 20170331 6

A series of novel 2-oxo-quinoline derivatives containing α-aminophosphonates were designed and synthesized as antitumor agents. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay results demonstrated that some compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3 and NCI-H460 tumor cell lines, and most compounds showed much lower cytotoxicity against HL-7702 normal cells than 5-FU and cisplatin. The action mechanism of representative compound <b>5b ...[more]

PMID: 30108826

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