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

Abstract

Summary 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 μmol/L of EC50 whereas standard GTN produced 975.8 μmol/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.

Inflammation, Nitro-Oxidative Stress, Impaired Autophagy, and Insulin Resistance as a Mechanistic Convergence Between Arterial Stiffness and Alzheimer’s Disease

“…Although being the smallest gaseous signaling molecule, NO is responsible for maintaining homeostasis in a myriad of tissues and molecular pathways (Balaiya and Chalam, 2014) and embodies a key role in the pathogenesis of inflammation, though it is a double-edged sword (Sharma et al, 2007). In normal physiological conditions, NO exerts an anti-inflammatory function (Sarkate et al, 2017;Sherikar et al, 2019;Zhang et al, 2020a) while NO is also considered a pro-inflammatory mediator in pathological conditions, such as arterial stiffness (Sindler et al, 2011;Isabelle et al, 2012;Aroor et al, 2018;Chiba et al, 2019) and AD (Cifuentes et al, 2017;Tang et al, 2019;Austin and Katusic, 2020;Dubey et al, 2020;Stefano et al, 2020) mainly due to its contribution in nitro-oxidative stress (Pérez-Torres et al, 2020; Figure 4).…”

Proteomic Assessment of C57BL/6 Hippocampi after Non-Selective Pharmacological Inhibition of Nitric Oxide Synthase Activity: Implications of Seizure-like Neuronal Hyperexcitability Followed by Tauopathy

“…NO is considered a double-edged sword, however. In normal physiological conditions, it exerts an anti-inflammatory function [ 11 , 12 ], while in cardiovascular pathology, i.e., arterial stiffness (AS) [ 13 , 14 ] and in neurodegenerative diseases [ 15 , 16 ], NO is also considered a pro-inflammatory mediator. Recently, there has been a growing interest in the potential mechanistic convergence between AS and neurodegenerative syndromes since epidemiological studies increasingly report an independent interplay between both pathologies [ 17 , 18 ].…”

Discovery of new cyanopyridine/chalcone hybrids as dual inhibitors of EGFR/BRAFV600E with promising antiproliferative properties

“…In addition, chalcones have been demonstrated to be a significant source for naturally present α and β-unsaturated ketones; they have numerous therapeutic properties, such as anti-inflammatory, [32] F I G U R E 1 Structures of compounds I-IV antibacterial, [33] antimalarial, [34] and anticancer activities. [35] Inhibition of angiogenesis, [36,37] reversal of multidrug resistance, [38] antiproliferative activity, [39] antimitotic effect, [40] and induction of apoptosis [41] in numerous cancer cell lines have all been proposed as mechanisms for the cytotoxic action of chalcone derivatives.…”