Abstract

Mohd. Imran* and Naira Nayeem

DOI : http://dx.doi.org/10.13005/ojc/320129

Four pyridazinones (2-5) were synthesized by the reaction of 3-benzoylpropionic acid with the corresponding hydrazines. These pyridazinones were further derivatized with appropriate aromatic aldehydes in the presence of piperidine to obtain the desired compounds (6-13). The chemical structures of the synthesized pyridazinones were elucidated on the basis of their spectral analysis (IR, ¹H-NMR, and ¹³C-NMR). Molecular docking studies were carried out to identify the most active antihypertensive pyridazinone compound by using the crystal structure of human Angiotensin Converting Enzyme (ACE), the enzyme implicated in the pathogenesis of hypertension. The compound (6) was identified as the most active inhibitor of the Angiotensin Converting Enzyme (ACE). This compound was further assessed for its ACE inhibitory activity using Dojindo ACE Kit-WST test kit. The enzymatic ACE inhibitory activity revealed that the compound (6) had IC₅₀ value of 5.78 μg/mL, wherein the standard drug Lisinopril had IC₅₀ value of 0.85 μg/mL. It has been concluded that incorporation of free amino groups and free carboxylic acid groups in the structure of the synthesized pyridazinone (6-13) may provide more active and potent ACE inhibitors.

Benzoylpropionic acid; Pyridazinones; Molecular modelling; ACE inhibitor; Antihypertyensive agents

[ View HTML Full Text]