尽管癌症仍是全球重要的死亡原因之一，但目前的癌症药物存在许多严重的副作用。因此需要新的抗癌药物来克服这些不足。交链孢属是最广泛的真菌之一，其中许多物种产生具有潜在多药理活性的多种代谢物。少数交链孢属的喹酮和吡喃酮已经被证明对某些癌细胞系具有细胞毒活性，但其分子作用方式尚不清楚。本研究旨在通过分子对接和动态模拟方法，探究来自交链孢菌及交链孢交替菌的少数喹酮和吡喃酮的抗癌活性潜力机制。筛选出的代谢物被用于检测它们与已知的抗癌靶蛋白热休克蛋白90（HSP90）的结合亲和力。分子对接研究显示，Macrosporin、Altersolanol B、Fonsecin和Neoaltenuene等化合物与目标蛋白具有良好的结合亲和力，并通过分子动力学模拟评估了它们所形成的复合物的稳定性。通过分子动力学模拟获得的均方根距离（RMSD）、均方根波动（RMSF）和主成分分析（PCA）图表的分析显示，在100 ns的时间内，所有四种引导分子与目标蛋白的复合物都是稳定的。分子力学泊松-泊兹曼表面积（MM-PBSA）计算用于计算结合自由能。利用无机模拟分析研究引导分子的吸收、分布、代谢、排泄和毒性（ADMET）以及物理化学性质，以确定它们的类药性。结果表明，Macrosporin、Fonsecin和Neoaltenuene具有成为有前途的以HSP90为靶点的抗癌分子的潜力。

Although cancer continues to be one of the world's major causes of death, current cancer drugs have many serious side effects. There remains a need for new anticancer agents to overcome these shortcomings. Alternaria is one of the most widespread fungal genera, many species of which produce several classes of metabolites with potential polypharmacological activities. A few quinones and pyrones from Alternaria spp. have proven to exert cytotoxic effects against certain cancer cell lines, but their molecular mode of action is not known. The current study aimed to investigate the potential mechanisms that underlie the anticancer activity of a few selected quinones and pyrones from Alternaria solani and Alternaria alternata by molecular docking and dynamic simulation approaches. The selected metabolites were screened for their binding affinity to Heat shock protein 90 (HSP90), which is a known anticancer drug target. Molecular docking studies have revealed that Macrosporin, Altersolanol B, Fonsecin, and Neoaltenuene have good binding affinities with the target protein and the stabilities of the formed complexes were evaluated through molecular dynamics simulations. By analyzing the Root Mean Square Distance (RMSD), Root Mean Square Fluctuation (RMSF), and Principal Component Analysis (PCA) plots obtained from molecular dynamics simulations, this study shows that the complexes of all 4 lead molecules with target protein are stable over a 100 ns period. Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations were used to compute the binding free energies. The lead molecules were studied using in-silico analysis to determine their drug-likeness based on their Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) and physicochemical properties. The results demonstrate that Macrosporin, Fonsecin, and Neoaltenuene could become promising anticancer molecules that target HSP90.Communicated by Ramaswamy H. Sarma.