Discovery and optimization of novel dual dithiocarbamates as potent anticancer agents

European Journal of Medicinal Chemistry
Ri-Dong LiRun-Tao Li

Abstract

A series of dual dithiocarbamates were synthesized and evaluated for their in-vitro anticancer activities on human non-small cell lung cancer cell line H460. Nine compounds exhibited significant antiproliferative activities with IC50 less than 1 μM. Among them, compound 14m showed the highest inhibitory activity against H460 cell and inhibited the growth of nine types of tumor cells with IC50 values less than 1 μM. It also achieved IC50 of 54 nM and 23 nM against HepG2 and MCF-7 cell lines, respectively. Preliminary structure-activity relationship study indicated that: a) when the methyl group (region A) is substituted with benzene rings, ortho substitution on the benzene ring is favored for activity; b) substitution with heterocyclic structures at region A exhibited greater impact on the anti-tumor activity of compounds, in which pyridine ring, thiazole ring, coumarin and benzo[b]thiophene are favored and quinoline ring is the most favored; c) substitution with different amines (region B) also showed marked effect on the activity of compounds and dimethylamine and morpholine are preferred to other tested amines.

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Citations

Feb 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ahmed MalkiHayam Ashour
Sep 14, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Yahui DingQuan Zhang
Mar 10, 2016·Acta Crystallographica. Section E, Crystallographic Communications·Muzzaffar A BhatJan Wikaira
Jun 27, 2020·The Journal of International Medical Research·Jie ChenHong-Mei Yang
Feb 10, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Heping ZhuYuanjiang Pan
Oct 20, 2020·Bioorganic Chemistry·Sangita Dattatray ShindeNagula Shankaraiah
May 29, 2021·Chemical Biology & Drug Design·Usman GhaniZafer Asim Kaplancikli

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