One-Pot Synthesis and Bioevaluation of Hexahydroquinoline-3-carboxamide Derivatives as Potential Antibacterial and Antifungal Agents
摘要
A series of hexahydroquinoline-3-carboxamide derivatives 4a–4j were prepared via an L-proline-catalyzed one-pot multicomponent reaction involving substituted aromatic aldehydes, dimedone, and N-aryl-3-oxobutanamides in ethanol, providing the target molecules in good yields (69–89%) under mild conditions. Structural confirmation was achieved using IR, 1H and 13C NMR, and mass spectrometry. Antimicrobial evaluation by the minimum inhibitory concentration (MIC) assay revealed that compounds 4c, 4f, 4h, and 4i possessed notable antibacterial activity (MIC = 62.5–250 μg/mL), particularly against Escherichia coli, while generally moderate activity was observed against Gram-positive strains. The results indicate that structural variations strongly influenced biological potency, with electron-withdrawing groups on the aromatic rings enhancing the activity against Gram-negative bacteria. Compound 4c emerged as a promising lead scaffold. The study underscores the value of L-proline-catalyzed one-pot synthesis as a sustainable approach for generating bioactive heterocycles. These findings demonstrate that the synthesized derivatives hold potential for further optimization toward new antimicrobial agents.