Fatty acid metabolism protein (FadR) is the most common and imperative biological target in E. coli, therefore inhibition of this molecular target by designed inhibitor will result in effective inhibition of microbial growth by crippling the metabolic functioning machinery. The present research aimed at exploring the FadR inhibitory potential of two furan-2-yl compounds; (E)-methyl-5-((3R,4R,6S,7R)-3-(2-(furan-2-yl)ethyl)-7-hydroxy-4-(3-methylbut-2-enyl)-octahydro-2H-chromen-6-yl)-4-methylpent-4-enoate (1) and methyl 3-((4aR,7S,8aR)-7-((3S,4R,E)-1-(furan-2-yl)-3-(hydroxymethyl)-7-methyloct-5-en-4-yl)-3,4,4a,5,6,7,8,8a-octahydronaphthalen-2-yl)propanoate (2) employing molecular docking studies against the target (PDB ID: 1H9G), by utilizing the Glide module of the Maestro 9.1 software. The best pose of compound 2 stated the most effective FadR inhibition with Glide score of -13.68 Kcal/mol whereas the score of compound 1 was found to be -13.23 Kcal/mol. Based on the crystal structure of the molecular target, the compound 2 formed a strong hydrogen bond with Asp145 via hydroxyl-group of the furan moiety in docking complex whereas the branched oxygen atom present in the hydroxyl group of compound 2 made hydrogen bonding with the amino acid residue Leu165. The water molecule present in the protein also formed hydrogen bonding with the Asp145. From this study, it can be concluded that the furan-2-yl containing compounds hold the potential to exhibit bacteriocidal activity by disrupting the fatty acid beta-oxidation and enzyme expression in fatty acid biosynthesis process when the key target fatty acid metabolism protein enzyme (FadR) was blocked successfully.
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