Identification of Microbial-Based Natural Products as Potential CYP51 Inhibitors for Eumycetoma Treatment: Insights from Molecular Docking, MM-GBSA Calculations, ADMET Analysis, and Molecular Dynamics Simulations DOI Creative Commons
Tilal Elsaman, Mohamed Khalid Alhaj Awadalla, Malik Suliman Mohamed

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 598 - 598

Published: April 20, 2025

Background/Objectives: Eumycetoma, caused by Madurella mycetomatis, is a chronic fungal infection with limited treatment options and increasing drug resistance. CYP51, key enzyme in ergosterol biosynthesis, well-established target for azole antifungals. However, existing drugs demonstrate efficacy treating eumycetoma. Microbial-based natural products, their structural diversity bioactivity, offer promising source novel CYP51 inhibitors. This study aimed to identify potential mycetomatis inhibitors from microbial products using molecular docking, MM-GBSA calculations, ADMET analysis, dynamics (MD) simulations. Methods: Virtual screening was conducted on library of microbial-based an in-house homology model itraconazole as the reference drug. The top compounds initial docking were refined through Standard Extra Precision docking. calculations assessed binding affinities, analysis evaluated drug-like properties. Compounds favorable properties underwent MD Results: computational investigations identified 34 better scores affinity than itraconazole. Of these, 9 interacted heme group residues active site CYP51. In silico pharmacokinetic profiling 3 candidates, simulations confirmed Conclusions: highlights microbial-derived particularly monacyclinone G, H, I, candidates inhibition, eumycetoma, requiring further experimental validation.

Language: Английский

Quality of Life, Disability, and Fungal Neglected Tropical Diseases DOI
Alyson M. Cavanaugh, Amanda Ribeiro dos Santos, Dayvison Francis Saraiva Freitas

et al.

Current Fungal Infection Reports, Journal Year: 2025, Volume and Issue: 19(1)

Published: April 9, 2025

Language: Английский

Citations

0
Identification of Microbial-Based Natural Products as Potential CYP51 Inhibitors for Eumycetoma Treatment: Insights from Molecular Docking, MM-GBSA Calculations, ADMET Analysis, and Molecular Dynamics Simulations DOI Creative Commons
Tilal Elsaman, Mohamed Khalid Alhaj Awadalla, Malik Suliman Mohamed

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 598 - 598

Published: April 20, 2025

Background/Objectives: Eumycetoma, caused by Madurella mycetomatis, is a chronic fungal infection with limited treatment options and increasing drug resistance. CYP51, key enzyme in ergosterol biosynthesis, well-established target for azole antifungals. However, existing drugs demonstrate efficacy treating eumycetoma. Microbial-based natural products, their structural diversity bioactivity, offer promising source novel CYP51 inhibitors. This study aimed to identify potential mycetomatis inhibitors from microbial products using molecular docking, MM-GBSA calculations, ADMET analysis, dynamics (MD) simulations. Methods: Virtual screening was conducted on library of microbial-based an in-house homology model itraconazole as the reference drug. The top compounds initial docking were refined through Standard Extra Precision docking. calculations assessed binding affinities, analysis evaluated drug-like properties. Compounds favorable properties underwent MD Results: computational investigations identified 34 better scores affinity than itraconazole. Of these, 9 interacted heme group residues active site CYP51. In silico pharmacokinetic profiling 3 candidates, simulations confirmed Conclusions: highlights microbial-derived particularly monacyclinone G, H, I, candidates inhibition, eumycetoma, requiring further experimental validation.

Language: Английский

Citations

0