Screening potential inhibitor from actinomycetes for Dihydrofolate reductase of Staphylococcus aureus – In vitro and in silico studies

Abstract

Cellulitis is a skin disease which is caused by the pathogen Staphylococcus aureus. The protein Dihydrofolate reductase is an important drug based target for Trimethoprim. Dihydrofolate reductase is reversibly inhibited by the drug trimethoprim. One of the major enzymes responsible for converting dihydrofolic acid into tetrahydrofolic acid. The screening of microbial natural products, Soil isolation is a rich source of actinomycetes. The actinomycetes sp. KK21-2 strain isolated from the soil, the aqueous extract of the isolates yielded 33 active metabolites from the LC-MS analysis. Based on the ADMETox analysis, 8 compounds were excluded and finally 25 compounds were selected for the docking analysis. Protein structure of S. aureus retrieved from PDB, drug and compounds were obtained from the PubChem Database. Molecular docking (XP) and Induced Fit Docking (IFD) were completed utilizing the Glide Module of Schrodinger. Molecular dynamics simulation employing the Schrodinger Desmond module was used to examine the stability of the docked complex. From the results of docking analysis and MD Simulation result 5-(3,4-Dihydroxy-1,5-cyclohexadien-1-yl) phenylhydantoin have suggest this compound have multi- targeting potency against the cellulitis skin disease from the pathogen Staphylococcus aureus, in future need to be verified through in vitro and in vivo analysis.

Keywords

• Actinomycetes
• Cellulitis
• Staphylococcus aureus
• Molecular docking
• Dihydrofolate reductase
• MD simulation