title: Interaction of 5-(2, 4-dimethylbenzyl) pyrrolidin-2-one with selected antifungal drug target enzymes by in silico molecular docking studies.
abstract: Currently the criteria used for selecting optimal new antifungal drug candidates include inhibitors of fungal cell wall biosynthesis, essential reaction and pathways. In silico approach resulting in the identification of essential reactions and pathways spreads across several parts of metabolism. The aim of the present study was to study the interaction of the isolated anti-Aspergillus compound, 5-(2, 4-dimethylbenzyl) pyrrolidin-2-one (DMBPO) from a novel Streptomyces VITSVK5 spp. with 6 selected antifungal drug target enzymes by in silico molecular docking approach. The compound DMBPO showed minimum binding energy (-6.66 kcal/mol) with 14 alpha-sterol demethylase (cyp51), (-5.65 kcal/mol) with Rubythrine, and (-4.43 kcal/mol) with β-1-3 Glucan binding protein. Two enzymes 14 alpha-sterol demethylase (cyp51) and β-1-3 Glucan were reported to be mostly responsible for drug resistance in Aspergillus species. The compound DMBPO interacted with several amino acid residues, of which leucine was found to be common among all the target enzymes for protein and hydrogen bond formation. Our results suggest that DMBPO could target Aspergillus fungal proteins to exhibit anti-Aspergillus activity in drug resistant strains.
authors.affiliation: Biomolecules and Genetics Division, School of Biosciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India.
authors.forename: Kumar
authors.initials: K
authors.lastname: Saurav
authors.forename: K
authors.initials: K
authors.lastname: Kannabiran
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects / Q000201:enzymology*; D019295:Computational Biology / Q000379:methods*; D004798:Enzymes / Q000378:metabolism*; D008958:Models, Molecular; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology*; D047071:beta-Glucans / Q000737:chemistry
chemical_list: C571387:5-(2,4-dimethylbenzyl)pyrrolidin-2-one; D000935:Antifungal Agents; D004798:Enzymes; D011760:Pyrrolidinones; D047071:beta-Glucans; C033363:beta-1,3-glucan