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Dihydropyrazole Derivatives Containing Benzo Oxygen Heterocycle and Sulfonamide Moieties Selectively and Potently Inhibit COX-2: Design, Synthesis, and Anti-Colon Cancer Activity Evaluation

Authors :
Xiao-Qiang Yan
Zhong-Chang Wang
Bo Zhang
Peng-Fei Qi
Gui-Gen Li
Hai-Liang Zhu
Source :
Molecules, Vol 24, Iss 9, p 1685 (2019)
Publication Year :
2019
Publisher :
MDPI AG, 2019.

Abstract

Cyclooxygenase-2 (COX-2) as a rate-limiting metabolism enzyme of arachidonic acid has been found to be implicated in tumor occurrence, angiogenesis, metastasis as well as apoptosis inhibition, regarded as an attractive therapeutic target for cancer therapy. In our research, a series of dihydropyrazole derivatives containing benzo oxygen heterocycle and sulfonamide moieties were designed as highly potent and selective COX-2 inhibitors by computer-aided drug analysis of known COX-2 inhibitors. A total of 26 compounds were synthesized and evaluated COX-2 inhibition and pharmacological efficiency both in vitro and in vivo with multi-angle of view. Among them, compound 4b exhibited most excellent anti-proliferation activities against SW620 cells with IC50 of 0.86 ± 0.02 µM than Celecoxib (IC50 = 1.29 ± 0.04 µM). The results favored our rational design intention and provides compound 4b as an effective COX-2 inhibitor available for the development of colon tumor therapeutics.

Details

Language :
English
ISSN :
14203049 and 24091685
Volume :
24
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.51905b38f2064d27810f32cc134e1b64
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules24091685