Department of Biomedical Engineering, Islamic University, Kushtia, 7003, Bangladesh.
Department of Pharmacy, Islamic University, Kushtia, 7003, Bangladesh.
Curr Microbiol. 2024 Mar 12;81(5):113. doi: 10.1007/s00284-024-03621-z.
During this coronavirus pandemic, when a lot of people are already severely afflicted with SARS-CoV-19, the dispersion of black fungus is making it worse, especially in the Indian subcontinent. Considering this situation, the idea for an in silico study to identify the potential inhibitor against black fungal infection is envisioned and computational analysis has been conducted with isatin derivatives that exhibit considerable antifungal activity. Through this in silico study, several pharmacokinetics properties like absorption, distribution, metabolism, excretion, and toxicity (ADMET) are estimated for various derivatives. Lipinski rules have been used to observe the drug likeliness property, and to study the electronic properties of the molecules, quantum mechanism was analyzed using the density functional theory (DFT). After applying molecular docking of the isatin derivatives with sterol 14-alpha demethylase enzyme of black fungus, a far higher docking affinity score has been observed for the isatin sulfonamide-34 (derivative 1) than the standard fluconazole. Lastly, molecular dynamic (MD) simulation has been performed for 100 ns to examine the stability of the proposed drug complex by estimating Root Mean Square Deviation (RMSD), Radius of gyration (Rg), Solvent accessible surface area (SASA), Root Mean Square Fluctuation (RMSF), as well as hydrogen bond. Listed ligands have precisely satisfied every pharmacokinetics requirement for a qualified drug candidate and they are non-toxic, non-carcinogenic, and have high stability. This natural molecule known as isatin derivative 1 has shown the potential of being a drug for fungal treatment. However, the impact of the chemicals on living cells requires more investigation and research.
在这次冠状病毒大流行期间,当许多人已经受到严重的 SARS-CoV-19 感染时,黑木耳的传播使情况变得更糟,特别是在印度次大陆。考虑到这种情况,我们设想了一项计算机模拟研究,以确定针对黑曲霉感染的潜在抑制剂,并对具有相当抗真菌活性的靛红衍生物进行了计算分析。通过这项计算机模拟研究,对各种衍生物的一些药代动力学特性(如吸收、分布、代谢、排泄和毒性(ADMET))进行了估计。使用 Lipinski 规则观察药物相似性特性,并使用密度泛函理论(DFT)分析分子的电子性质。在用黑曲霉固醇 14-α 去甲基化酶对靛红衍生物进行分子对接后,发现靛红磺酰胺-34(衍生物 1)与标准氟康唑相比具有更高的对接亲和力评分。最后,进行了 100ns 的分子动力学(MD)模拟,通过估计均方根偏差(RMSD)、回转半径(Rg)、溶剂可及表面积(SASA)、均方根波动(RMSF)以及氢键来检查所提出的药物复合物的稳定性。列出的配体完全满足合格药物候选物的所有药代动力学要求,它们是非毒性、非致癌性且稳定性高的。这种被称为靛红衍生物 1 的天然分子显示出作为真菌治疗药物的潜力。然而,这些化学物质对活细胞的影响需要更多的调查和研究。