Synthesis and Biological Study of Some New α-amidoalkylated Azole and Azine Derivatives

Abstract

Heterocyclic compounds, particularly azoles and azines, represent cornerstones of modern medicinal chemistry due to their profound biological activities. This study describes the efficient synthesis of a novel series of α-amidoalkylated derivatives, hybrid molecules incorporating these privileged heterocyclic systems. The targeted compounds were successfully prepared via a versatile and operationally simple one-pot α-amidoalkylation reaction, utilizing N-acyliminium ion chemistry as a key strategic approach. A diverse library of compounds was synthesized in good to excellent yields, and their structures were unequivocally confirmed by comprehensive spectroscopic techniques, including IR, 1H NMR, 13C NMR, and mass spectrometry. All synthesized derivatives were evaluated for their in vitro biological potential. The screening revealed significant antimicrobial activity against a panel of Gram-positive and Gram-negative bacterial strains, as well as fungal pathogens, with several compounds exhibiting promising Minimum Inhibitory Concentration (MIC) values. Furthermore, selected compounds demonstrated potent cytotoxic effects against human cancer cell lines (MCF-7 and A549), as determined by the MTT assay, while showing comparatively lower toxicity towards normal human embryonic kidney (HEK-293) cells, indicating a degree of selective toxicity. A preliminary structure-activity relationship (SAR) analysis was established, identifying the nature of the heterocyclic core (azole vs. azine) and the substituents on the amidoalkyl side chain as critical determinants for biological potency. These findings position the novel α-amidoalkylated azole and azine derivatives as promising lead compounds for the further development of new antimicrobial and anticancer agents.