Synthesis and antimicrobial activity mechanism of N-substituted methyl Matrinecarboxylate derivatives

To address the crisis of multidrug-resistant microbial infections, this study used matrine, a natural product, as the lead compound to design and synthesize a series of novel N-substituted methyl matrinecarboxylate derivatives. Antimicrobial evaluation showed that multiple compounds exhibited potent inhibitory activity against Candida albicans. Among them, the minimum inhibitory concentration (MIC) of compound 4r reached 1.6 μg/mL, and it could effectively inhibit and destroy the biofilm of Candida albicans. The mechanism study indicated that compound 4r could bind stably to the target protein, and molecular dynamics simulations confirmed the stability of the complex. Further analysis of the 3D-QSAR model revealed that steric and hydrophobic interactions were the key factors affecting the activity. This work provides valuable design ideas and experimental basis for the development of novel Antifungal lead compounds based on natural products.

3D-QSAR; Antimicrobial activity; Biofilm; Candida albicans; Molecular docking; N-substituted methyl matrinecarboxylate derivatives.