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

The main aim of this work is to find out novel chemical moieties with potent anti-inflammatory and vasorelaxant activities with reduced gastric toxicities. For fulfilling the above aim, here we investigated novel chalcones (1, 3-diphenylprop-2-en-1-one derivatives) with nitric oxide (NO) and hydrogen sulphide (H2S) donating potency for anti-inflammatory activity by carrageenan-induced rat paw oedema. These molecules then further evaluated for in-vitro NO-releasing potency and vasorelaxation effect on isolated adult goat aortic tissue. The promising molecules were further screened for ulcerogenic activity in the rat model. The tested compounds produced % inhibition in paw oedema ranging from 29.16% to 79.69% and standard drug Diclofenac sodium produced 85.30% reduction in paw oedema after 5 hours. Out of this dataset, compounds AI1, AI7, Ca1, B2, B10, D2, and E8 showed 73.01%, 79.69%, 75.02%, 75.46%, 74.35%, 73.9% and 74.35% reduction in paw oedema respectively, which is approximately 80%-90% to that of standard Diclofenac sodium. The compound Ca1 was found to release 0.870 +/- 0.025 mol/mol of NO and standard Glyceryl trinitrate (GTN) was found to release 0.983 +/- 0.063 mol/mol of NO. The compound Ca1 produced 950.2 mu mol/L of EC50 whereas standard GTN produced 975.8 mu mol/L of EC50 for aortic smooth relaxation. The compounds Ca1 produced 0.1117 of ulcer index which is far less than that of standard Diclofenac sodium (1.148). The potent lead molecules were further evaluated to understand the mechanism of vasorelaxation by using specific antagonists or blockers of NO and H2S.