Gupta Shiv Shankar, Kesarwani Veerbhan, Shankar Ravi, Sharma Upendra
C-H Activation & Phytochemistry Lab, Chemical Technology Division, CSIR-IHBT, Palampur, HP 176061 India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002 India.
In Silico Pharmacol. 2025 May 5;13(2):74. doi: 10.1007/s40203-025-00359-9. eCollection 2025.
Fungal infections caused by pose a significant global health challenge due to their high morbidity, mortality, and the growing prevalence of drug resistance. The failure of existing antifungal agents against resistant strains underscores the urgent need for novel therapeutic alternatives. In response to this challenge, we have created an in-house library of biologically relevant nitrogenous heterocycles to screen against the resistant dihydrofolate reductase (DHFR), with the aim of identifying potential antifungal leads. Using computational tools such as molecular docking and dynamics simulations, we identified two promising leads based on isoquinoline scaffold. The stability of these leads was further assessed using quantum chemical descriptor calculations. Screening results indicate that these isoquinoline-based compounds could serve as potential antifungal candidates, offering a foundation for the development of new therapies to combat resistant infections. Further experimental studies, including animal model testing, are necessary to validate and confirm our findings.
The online version contains supplementary material available at 10.1007/s40203-025-00359-9.
由 引起的真菌感染因其高发病率、高死亡率以及耐药性的日益普遍而构成重大的全球健康挑战。现有抗真菌药物对耐药菌株失效凸显了对新型治疗替代品的迫切需求。为应对这一挑战，我们创建了一个内部生物相关含氮杂环化合物库，以筛选耐药 二氢叶酸还原酶（DHFR），目的是确定潜在的抗真菌先导物。使用分子对接和动力学模拟等计算工具，我们基于异喹啉支架确定了两个有前景的先导物。使用量子化学描述符计算进一步评估了这些先导物的稳定性。筛选结果表明，这些基于异喹啉的化合物可作为潜在的抗真菌候选物，为开发对抗耐药 感染的新疗法奠定了基础。需要进一步的实验研究，包括动物模型测试，以验证和确认我们的发现。
在线版本包含可在10.1007/s40203-025-00359-9获取的补充材料。
