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Tytuł pozycji:

In silico prediction of Antifungal compounds from Natural sources towards Lanosterol 14-alpha demethylase (CYP51) using Molecular docking and Molecular dynamic simulation.

Tytuł:
In silico prediction of Antifungal compounds from Natural sources towards Lanosterol 14-alpha demethylase (CYP51) using Molecular docking and Molecular dynamic simulation.
Autorzy:
Sama-Ae I; School of Allied Health Sciences, Walailak University, 80161, Nakhon Si Thammarat, Thailand.
Pattaranggoon NC; Program in Bioinformatics and Computational Biology, Chulalongkorn University, 10330, Bangkok, Thailand.
Tedasen A; School of Allied Health Sciences, Walailak University, 80161, Nakhon Si Thammarat, Thailand; Research Excellence Center for Innovation and Health Product, Walailak University, 80161, Nakhon Si Thammarat, Thailand. Electronic address: .
Źródło:
Journal of molecular graphics & modelling [J Mol Graph Model] 2023 Jun; Vol. 121, pp. 108435. Date of Electronic Publication: 2023 Feb 16.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: New York, NY : Elsevier Science, Inc., c1997-
MeSH Terms:
Antifungal Agents*/pharmacology
Antifungal Agents*/chemistry
Molecular Dynamics Simulation*
Molecular Docking Simulation ; Sterol 14-Demethylase/chemistry ; Sterol 14-Demethylase/metabolism ; Sterol 14-Demethylase/pharmacology ; Lanosterol/pharmacology ; Candida albicans ; Microbial Sensitivity Tests
Contributed Indexing:
Keywords: ADMET; Anti-fungal; Lanosterol 14-alpha demethylase; Molecular docking analysis; Molecular dynamics simulation
Substance Nomenclature:
0 (Antifungal Agents)
EC 1.14.14.154 (Sterol 14-Demethylase)
1J05Z83K3M (Lanosterol)
Entry Date(s):
Date Created: 20230227 Date Completed: 20230410 Latest Revision: 20230613
Update Code:
20240105
DOI:
10.1016/j.jmgm.2023.108435
PMID:
36848730
Czasopismo naukowe
An increase in the occurrence of fungal infections throughout the world, as well as the rise of novel fungal strains and antifungal resistance to commercially available drugs, suggests that new therapeutic choices for fungal infections are needed. The purpose of this research was to find new antifungal candidates or leads of secondary metabolites derived from natural sources that could effectively inhibit the enzymatic activity of Candida albicans lanosterol 14-alpha demethylase (CYP51) while also having good pharmacokinetics. In silico prediction of the drug-likeness, chemo-informatics and enzyme inhibition indicate that the 46 compounds derived from fungi, sponges, plants, bacteria and algae sources have a high novelty to meet all five requirements of Lipinski's rules and impede enzymatic function. Among the 15 candidate molecules with strong binding affinity to CYP51 investigated by molecular docking simulation, didymellamide A-E compounds demonstrated the strongest binding energy against the target protein at -11.14, -11.46, -11.98, -11.98, and -11.50 kcal/mol, respectively. Didymellamide molecules bind to comparable active pocket sites of antifungal ketoconazole and itraconazole medicines by hydrogen bonds forming to Tyr132, Ser378, Met508, His377 and Ser507, and hydrophobic interactions with HEM601 molecule. The stability of the CYP51-ligand complexes was further investigated using molecular dynamics simulations that took into account different geometric features and computed binding free energy. Using the pkCSM ADMET descriptors tool, several pharmacokinetic characteristics and the toxicity of candidate compounds were assessed. The findings of this study revealed that didymellamides could be a promising inhibitor against these CYP51 protein. However, there is still a need for further in vivo and in vitro studies to support these findings.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)

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