Synthesis, docking studies andin vitroevaluation of novel chalcones as potent inhibitors of phosphodiesterase 5 from human platelets and 5A from bovine recombinant

Abstract

Chalcones with a nitric oxide (NO) donating scaffold and a variety of substituents were synthesized. A docking study was performed and molecules were evaluated for in vitro phosphodiesterase 5 and 5A inhibitory potency.

Investigation of anti‐inflammatory, nitric oxide donating, vasorelaxation and ulcerogenic activities of 1, 3‐diphenylprop‐2‐en‐1‐one derivatives in animal models

“…We have already reported the virtual screening and docking study of some of these molecules with COX‐ I and II in Sherikar et al . From all these previously reported molecules, series G1–G8 has H 2 S donating moiety ie 1, 2‐dithiole‐3‐thione and rest of compounds donates NO as they contain either nitrate esters or nitrate amides or phenyl nitrate moiety …”

“…Carboxymethylcellulose (CMC) and dimethyl sulphoxide (DMSO) were from Loba Chemie. All the screened compounds were reported in our previous articles with their synthesis, characterization and virtual screening.…”

“…[42][43][44][45][46][47] The compounds such as organic nitrates, nitrites, Cyclooxygenase (COX) inhibiting nitric oxide donators (CINODs) and H 2 S donating NSAIDs were extensively studied and reported as potent molecules for vasorelaxation, having anti-inflammatory potency with reduced gastric toxicities. 48,49 The NO and H 2 S donating chalcones were also reported to have PDE inhibitory potency [50][51][52] which is crucial for cGMP action as PDE causes hydrolysis of cGMP to GMP and inhibit NO-mediated vasorelaxation. All the above-reported data of NO and H 2 S donor are very significant and relevant since both these endogenous gases are having a direct or indirect effect on the vascular system.…”