Li Yufang, Kowah Jamal A H, Jiang Meiyan, Wu Yaqing, Wang Lisheng, Yang Fangfang
School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.
School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.
Bioorg Med Chem Lett. 2024 Apr 1;102:129671. doi: 10.1016/j.bmcl.2024.129671. Epub 2024 Feb 21.
Matrine and indole have antibacterial, anticancer, and other biological activities, in order to develop new antibiotics to solve the problem of multi-drug resistant bacteria. In this paper, we synthesized a series of 29 novel matrine derivatives as potential drug candidates by combining indole analogs and matrine. The antibacterial activity of these compounds was evaluated through minimum inhibitory concentration (MIC) assays against five bacterial strains (S. aureus, C. albicans, P. acnes, P. aeruginosa, and E. coli). The obtained results demonstrated promising antibacterial efficacy, particularly for compounds A20 and A18, which exhibited MIC values of 0.021 and 0.031 mg/ml, respectively, against S. aureus. Moreover, compounds A20 and A27 displayed remarkable MIC values of 2.806 and 4.519 mg/ml, respectively, against C. albicans, surpassing the performance of the clinical antibiotic penicillin G sodium (0.0368 mg/ml) and fluconazole (4.849 mg/ml). These findings underscore the significant bacteriostatic activity of the matrine derivatives. Furthermore, to gain a deeper understanding 3D-QSAR modeling was employed, revealing the critical influence of steric structure, charge distribution, hydrophobic interactions, and hydrogen bonding within the molecular structure on the bacteriostatic activity of the compounds. Additionally, molecular docking simulations shed light on the interaction between compound A20 and bacterial proteins, highlighting the involvement of hydrogen bonding, hydrophobic interactions, and π-π conjugation in the formation of stable complexes that inhibit the normal functioning of the proteins. This comprehensive analysis provided valuable insights into the antibacterial mechanism of the novel matrine derivatives, offering theoretical support for their potential application as antibiotics.
苦参碱和吲哚具有抗菌、抗癌等生物活性，旨在开发新型抗生素以解决多重耐药菌问题。本文通过将吲哚类似物与苦参碱结合，合成了一系列29种新型苦参碱衍生物作为潜在的候选药物。通过对五种细菌菌株（金黄色葡萄球菌、白色念珠菌、痤疮丙酸杆菌、铜绿假单胞菌和大肠杆菌）进行最低抑菌浓度（MIC）测定，评估了这些化合物的抗菌活性。所得结果显示出有前景的抗菌效果，特别是化合物A20和A18，它们对金黄色葡萄球菌的MIC值分别为0.021和0.031mg/ml。此外，化合物A20和A27对白色念珠菌的MIC值分别为2.806和4.519mg/ml，超过了临床抗生素青霉素G钠（0.0368mg/ml）和氟康唑（4.849mg/ml）的性能。这些发现强调了苦参碱衍生物具有显著的抑菌活性。此外，为了更深入了解，采用了3D-QSAR建模，揭示了分子结构中的空间结构、电荷分布、疏水相互作用和氢键对化合物抑菌活性的关键影响。此外，分子对接模拟揭示了化合物A20与细菌蛋白之间的相互作用，突出了氢键、疏水相互作用和π-π共轭在形成抑制蛋白正常功能的稳定复合物中的作用。这种全面分析为新型苦参碱衍生物的抗菌机制提供了有价值的见解，为其作为抗生素的潜在应用提供了理论支持。
