Design, synthesis and evaluation of benzenesulfonamide-substituted 1,5-diarylpyrazoles containing phenylacetohydrazide derivatives as COX-1/COX-2 agents against solid tumors

Abstract

Novel benzenesulfonamide-substituted 1,5-diarylpyrazoles containing phenylacetohydrazide derivatives have been synthesized. Among them, 48 showed best antiproliferative activity against A549 cells and was evaluated as a selective COX-2 inhibitor.

(E)-5-(4-Methoxyphenyl)-N′-(2-oxoindolin-3-ylidene)-1-phenyl-1H-pyrazole-3-carbohydrazide

“…In both molecules, the indole-2-one, formohydrazide and pyrazole groups are close to coplanar: the twist angles M 1 A/ M 1 B and M 1 B/M 1 C are 5.0 (1) and 10. (Lu et al, 2016). Intramolecular N-HÁ Á ÁO hydrogen bonds (Table 1) contribute to the observed molecular planarity.…”

Tuning the Dual Inhibition of Carbonic Anhydrase and Cyclooxygenase by Dihydrothiazole Benzensulfonamides

“…Thus, cytosolic forms (hCA I–III, VII), membrane-bound (hCA IV, IX, XII, and XIV), mitochondrial form (hCA V), and secreted (hCA VI) isozymes can be distinguished . The role of hCAs in the regulation of hypoxic-tumors pH has been extensively reported, ,− and isoforms II, IX, and XII are validated targets for cancer therapy. − On the other hand, the relevant role of hCOX 1 and 2 in different tumors has been outlined. − Celecoxib, a selective hCOX-2 inhibitor, has been approved by the FDA for adjuvant treatment of patients with familial adenomatous polyposis . Furthermore, the role of Aspirin as an adjuvant agent in the prevention and treatment of several solid tumors has been reported. − Furthermore, a COX-dependent evasion of immunity has been observed in tumors .…”