Phthalamide derivatives as ACE/AChE/BuChE inhibitors against cardiac hypertrophy: an in silico, in vitro, and in vivo modeling approach

This study aimed to synthesize three phthalamide derivatives (M-01, M-02, and M-03) and evaluate them as three-target (ACE/AChE/BuChE) inhibitors with the possible dual effect of reducing hypertension and r everting cardiac hypertrophy. After in silico and in vitro experiments, one compound was tested in vivo on rats. All three phthalamides were synthesized in good yields, showing good competitive inhibition of the three-target enzymes in silico and in vitro. M-01 (10 mg/kg) significantly reversed ca rdiomyocite hypertrophy (by 87.3%;p <  0.001) in the heart of spontaneous hypertensive rat (SHR) model. It was at least 18-fold more potent than the reference drug (captopril), which provided only 32.7% reversion. Three-target inhibitory activity was herein demonstrated for M-01, M-02, and M-03 in vitro and in silico, each with a simi lar effect. The compound tested in vivo (M-01) exhibited great potency in reducing hypertension and reverting cardiomyocyte hypertrophy, making it a promising candidate for further research.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research