Novel thiazole–pyrazolone hybrids as potent ACE inhibitors and their cardioprotective effect on isoproterenol‐induced myocardial infarction

Abstract

A facile synthesis of a group of novel thiazole-pyrazolone hybrids and their investigation for angiotensin-converting enzyme (ACE) inhibition are reported in this study. These compounds were synthesized using a well-known approach, based on the condensation of ethyl acetoacetate with thiazolylhydrazines, and characterized by various spectroscopic and analytical techniques. The entire set of compounds displayed a moderate-to-excellent inhibitory activity against ACE. In particular, compound 4i was found to be the most potent ACE inhibitor and was further studied for cardioprotective effects against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Compound 4i improved the cardiac function and prevented cardiac injury induced by ISO in Sprague Dawley rats. The levels of oxidative stress and proinflammatory cytokines were also restored to near normal by 4i as compared with the ISO group. In the Western blot analysis, compound 4i prevented mitochondrial apoptosis after MI by downregulating the expression of cleaved caspase-3 and Bax, with the upregulation of Bcl-2, as compared with the ISO group.

Pyrazolone-type compounds: synthesis andin silicoassessment of antiviral potential against key viral proteins of SARS-CoV-2

“… 43 Additionally, some pyrazolones were identified as potent inhibitors of angiotensin-converting enzyme (ACE), which has a number of pathological roles. 44 This prompted us to investigate the binding of selected pyrazolones to human ACE2 cell receptors, as well as to the spike RBD-ACE2 complex, with the idea that in such case, the SARS-CoV-2 cell entry and spreading could also be prevented.…”