Chinese Journal of Organic Chemistry >
Lead Optimization and Antiproliferative Activity Using a New Dithiocarbamates Substructure
Received date: 2018-01-02
Revised date: 2018-03-15
Online published: 2018-04-13
Supported by
Project supported by the National Natural Science Foundation of China (No. 201502063) and the Natural Science Foundation of Hubei Province (No. 2016CFB562).
In this work, a series of dithiocarbamate derivatives bearing diverse quinazolinones, benzoxazinones, and coumarin moieties were designed and synthesized via a one-pot three-component reaction. These compounds produced good yields and functioned quickly under mild conditions, and the desired products were readily isolated. Their in vitro antitumor activities were evaluated by the methyl thiazolyl tetrazolium (MTT) method against hepatoma carcinoma cells HCCLM-7, cervical carcinoma cells Hela, mammary adenocarcinoma cells MDA-MB-435S, colon carcinoma cells SW-480, laryngocarcinoma cells Hep-2, and mammary adenocarcinoma cells MCF-7. 3 compounds were identified as the most promising candidates, due to their high potency and broad-spectrum antiproliferative activity (IC50:3.5~13.5 μmol·L-1). The activities of some lead compounds were more than 10-fold more potent than that of positive control 5-fluorouracil (5-FU) (IC50:8.1~128.7 μmol·L-1). These results indicated that the dithiocarbamate (DTC) derivatives bearing fused heterocyclic moieties could be used as lead for further developing new antitumor active compounds.
Key words： dithiocarbamate; quinazolinone; benzoxazinone; coumarin; antiproliferative activity
Sun Haiyan , Sun Hongshun , Liu Mingzhen , Huang Wei , Yang Guangfu . Lead Optimization and Antiproliferative Activity Using a New Dithiocarbamates Substructure[J]. Chinese Journal of Organic Chemistry, 2018 , 38(8) : 2067 -2075 . DOI: 10.6023/cjoc201801001
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