Pharmacological Profiling and Toxicity Assessment of Newly Synthesized Antihypertensive Lead Compounds

Hypertension remains one of the most prevalent cardiovascular disorders worldwide and continues to drive the search for safer and more effective antihypertensive agents. In this study, a series of novel N-acylhydrazone and pyridazinone derivatives were designed and synthesized through rational molecular hybridization strategies. The compounds were subjected to comprehensive pharmacological profiling and toxicity assessment using integrated in silico, in vitro, and analytical approaches. Pharmacological evaluation demonstrated that several pyridazinone derivatives exhibited remarkable vasorelaxant potency, with effective concentration (EC₅₀) values significantly lower than the reference vasodilator hydralazine, alongside higher maximal relaxation responses. N-acylhydrazone derivatives showed moderate antihypertensive activity while retaining analgesic and anti-inflammatory properties. Structure–activity relationship (SAR) analysis revealed that specific substituents, such as furyl, nitro, and dimethylamino groups, contributed to enhanced bioactivity and improved pharmacological selectivity. Toxicity assessments, combining in silico ADMET predictions with in vitro cytotoxicity, hemolysis, and mutagenicity assays, confirmed that most compounds were non-mutagenic, exhibited low hepatotoxic potential, and maintained acceptable safety margins. Collectively, the findings highlight the translational promise of these newly synthesized scaffolds as antihypertensive lead candidates with improved efficacy and reduced adverse effects.