Department of Biochemistry & Forensic Science, University School of Sciences, Gujarat University, Ahmedabad, 380009, Gujarat, India.
Department of Microbiology & Biotechnology, University School of Sciences, Gujarat University, Ahmedabad, 380009, Gujarat, India.
Arch Biochem Biophys. 2021 Nov 15;712:109048. doi: 10.1016/j.abb.2021.109048. Epub 2021 Sep 30.
Like human, fungi too are known to share lot of structural similarities amongst their CYPs (Cytochrome P450 super family of enzymes) which allows antifungal 'azole' compounds to interact with CYPs of human. Clotrimazole, an 'azole' antifungal drug, is a known inhibitor of fungal CYP named CYP51B. Curcumin, a phytochemical obtained from Curcuma longa has the ability to interact with several different human CYPs to induce inhibition. The sequence and the structural similarities amongst both human and fungal CYPs suggest a strong possibility for curcumin to interact with fungal CYP51B to behave like an antifungal agent. To test this hypothesis a study was designed involving mucormycosis agent, Rhizopus oryzae. The ability of curcumin to interact with fungal CYP51B was analysed computationally through molecular docking, MM-GBSA and Molecular Dynamics (MD) simulation assessment. Further, interaction profile for fungal CYP51B-curcumin was compared with human CYP3A4-curcumin, as there are published evidence describing curcumin as an inhibitor of human CYPs. Additionally, to validate in silico findings, an in vitro assay was performed to examine the antifungal potentials of curcumin on the R. oryzae. Conclusive results allow us to determine a plausible mode of action of curcumin to act as an antifungal against a mucormycosis agent.
与人类一样，真菌的细胞色素 P450（细胞色素 P450 超家族酶）也有很多结构相似之处，这使得抗真菌“唑”类化合物能够与人类的细胞色素 P450 相互作用。克霉唑是一种“唑”类抗真菌药物，是一种已知的真菌 CYP51B 抑制剂。姜黄素是从姜黄中提取的一种植物化学物质，能够与几种不同的人类细胞色素 P450 相互作用，诱导抑制作用。人类和真菌细胞色素 P450 之间的序列和结构相似性表明，姜黄素很有可能与真菌 CYP51B 相互作用，表现出抗真菌作用。为了验证这一假设，设计了一项涉及毛霉病病原体——根霉的研究。通过分子对接、MM-GBSA 和分子动力学（MD）模拟评估，分析了姜黄素与真菌 CYP51B 相互作用的能力。此外，还比较了真菌 CYP51B-姜黄素与人类 CYP3A4-姜黄素的相互作用谱，因为有文献证据表明姜黄素是人类细胞色素 P450 的抑制剂。此外，为了验证计算机模拟结果，进行了体外实验来检测姜黄素对根霉的抗真菌潜力。最终的结果使我们能够确定姜黄素作为一种抗真菌剂对抗毛霉病病原体的可能作用模式。
