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Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition.
- Source :
-
Pharmacological Research . Feb2016, Vol. 104, p86-96. 11p. - Publication Year :
- 2016
-
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. Derivative 4d was identified as a potent COX-2 enzyme inhibitor and exerted an anticancer effect through COX-2 inhibition. Further investigation confirmed that 4d could induce A549 cell apoptosis and arrest the cell cycle at the G2/M phase. Moreover, treatment with 4d 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 of 4d suggests that this compound may be developed as a potential anticancer agent. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10436618
- Volume :
- 104
- Database :
- Academic Search Index
- Journal :
- Pharmacological Research
- Publication Type :
- Academic Journal
- Accession number :
- 113190035
- Full Text :
- https://doi.org/10.1016/j.phrs.2015.12.025