Islam Mazherul, Hossain Ahad, Yamari Imane, Abchir Oussama, Chtita Samir, Ali Ferdausi, Kawsar Sarkar M A
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong, 4331, Bangladesh.
Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, Morocco.
Chem Biodivers. 2024 Sep;21(9):e202400932. doi: 10.1002/cbdv.202400932. Epub 2024 Aug 16.
Carbohydrate derivatives play a crucial roles in biochemical and medicinal research, especially in the fields of chemistry and biochemistry. From this perspective, the present study was designed to explore the synthesis of methyl α-D-glucopyranoside derivatives (1-8), focusing on their efficacy against bacterial and fungal inhibition. The structure of the synthesized compounds was ascertained using FTIR, H-NMR, C-NMR, mass and elemental analyses. Antimicrobial screening revealed strong antifungal properties, with compound 7 exhibiting minimum inhibitory concentrations (MICs) ranging from 16-32 μg/L and minimum bactericidal concentrations (MBCs) ranging from 64-128 μg/L. Incorporating decanoyl acyl groups at C-2 and C-3 of (7) significantly improved the efficacy against bacteria and fungi. Structure-activity relationship (SAR) analysis indicated that adding nonanoyl and decanoyl groups to the ribose moiety enhanced potency against both bacterial and fungal strains. Computational methods, including molecular docking, density functional theory (DFT), Petra, Osiris, Molinspiration (POM) evaluation, and molecular dynamics (MD) simulations, were used to assess the efficacy of these derivatives. Compounds 6 and 7, which presented nonanoyl and decanoyl substituents, demonstrated greater efficacy. In addition, DFT studies identified compound 8 as possessing ideal electronic properties. Molecular docking revealed that compound 8 exhibits exceptional binding affinities to bacterial proteins, conferring potent antibacterial and antifungal activities. In addition, pharmacokinetic optimization via POM analysis highlighted compounds 1 and 2 as promising bioavailable drugs with minimal toxicity. Molecular dynamics simulations confirmed the stability of the 2-S. aureus complex, revealing the therapeutic potential of compounds 2 and 8. Future experiments are required to validate their efficacy for pharmaceutical development. The integration of in vitro and in silico methods, including DFT anchoring dynamics and molecular dynamics simulations, provides a solid framework for the advancement of effective anti-infective drugs.
碳水化合物衍生物在生物化学和医学研究中发挥着关键作用，尤其是在化学和生物化学领域。从这个角度来看，本研究旨在探索α-D-吡喃葡萄糖苷甲酯衍生物（1-8）的合成，重点关注它们对细菌和真菌的抑制效果。使用傅里叶变换红外光谱（FTIR）、氢核磁共振（H-NMR）、碳核磁共振（C-NMR）、质谱和元素分析确定了合成化合物的结构。抗菌筛选显示出强大的抗真菌特性，化合物7的最低抑菌浓度（MIC）范围为16-32μg/L，最低杀菌浓度（MBC）范围为64-128μg/L。在（7）的C-2和C-3位引入癸酰基显著提高了对细菌和真菌的抑制效果。构效关系（SAR）分析表明，在核糖部分添加壬酰基和癸酰基可增强对细菌和真菌菌株的效力。使用了包括分子对接、密度泛函理论（DFT）、Petra、Osiris、Molinspiration（POM）评估和分子动力学（MD）模拟在内的计算方法来评估这些衍生物的效果。具有壬酰基和癸酰基取代基的化合物6和7表现出更高的效果。此外，DFT研究确定化合物8具有理想的电子性质。分子对接显示化合物8对细菌蛋白具有特殊的结合亲和力，赋予其强大的抗菌和抗真菌活性。此外，通过POM分析进行的药代动力学优化突出了化合物1和2作为具有最小毒性的有前景的可生物利用药物。分子动力学模拟证实了2-金黄色葡萄球菌复合物的稳定性，揭示了化合物2和8的治疗潜力。未来需要进行实验来验证它们在药物开发中的效果。体外和计算机模拟方法的整合，包括DFT锚定动力学和分子动力学模拟，为开发有效的抗感染药物提供了坚实的框架。
