Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition. (February 2016)

• Record Type: Journal Article
• Authors: Qiu, Han-Yue; Wang, Peng-Fei; Li, Zhen; Ma, Jun-Ting; Wang, Xiao-Ming; Yang, Yong-Hua; Zhu, Hai-Liang
• Is Part Of: Pharmacological research. Volume 104(2016:Feb.)
• Page Start: 86
• Page End: 96
• Publication Date: 2016-02
• Subjects: Dihydropyrazole -- COX-2 selectivity -- Antitumor -- Diarylheterocycle; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2015.12.025
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: A series of novel COX-2 inhibitors was designed and synthesized as antitumor agents based on the knowledge of known COX-2 inhibitors and in silico scaffold modification strategy. Abstract: COX-2 has long been exploited in the treatment of inflammation and relief of pain; however, research increasingly suggests COX-2 inhibitors might possess potential benefits to thwart tumour processes. In the present study, we designed a series of novel COX-2 inhibitors based on analysis of known inhibitors combined with an in silico scaffold modification strategy. A docking simulation combined with a primary screen in vitro were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. Derivative4d was identified as a potent COX-2 enzyme inhibitor and exerted an anticancer effect through COX-2 inhibition. Further investigation confirmed that4d could induce A549 cell apoptosis and arrest the cell cycle at the G2/M phase. Moreover, treatment with4d reduced A549 cell adhesive ability and COX-2 expression. The morphological variation of treated cells was also visualized by confocal microscopy. Overall, the biological profile of4d suggests that this compound may be developed as a potential anticancer agent.