Molecular Docking Studies and In Silico ADMET Screening of New Chalcones as Lanosterol α-Demethylase and DNA Gyrase Topoisomerase B Inhibitors
Alok Singh Bharti Kumari, Sushil Kumar · Oriental Journal Of Chemistry · 2025
Chalcone and their benzotriazole derivatives originate from the nucleus ability to interpose into DNA base pairs, which inhibit lanosterol α-demethylase and DNA gyrase topoisomerase B. The active sites of topoisomerase B and lanosterol are the sites of molecular docking studies that provide comprehension of the intermolecular interactions for antimicrobial activity. Docking and ADMET properties of designed substituted benzaldehyde chalcones and their benzotriazoles using Schrodinger suit-2024 Maestro and SwissADME software programs against lanosterol α-demethylase and DNA gyrase topoisomerase B. C. albicans (lanosterol α-demethylase, PDB ID:4WMZ) and E. Coli (DNA gyrase topoisomerase B, PDB ID:1KZN) were selected for their respective binding affinities based on interaction patterns, GLIDE scores and docking scores. Compounds (7B1-7B7 and 9B1-9B3) showed strong binding interactions, and their ability to inhibit lanosterol α-demethylase (4WMZ) and DNA gyrase topoisomerase B (1KZN) for antimicrobial activity. Among the compounds, 9B1, 9B2, 9B3, and 7B1 have good binding affinity with GLIDE scores in the range of -10.655 to -10.154 against C. albicans and 7B1, 7B2 and 9B2 have good binding affinity with GLIDE score in range of -5.613 to -5.083 against E. coli when compared with the standard Fluconazole (-6.58) and Amoxicillin (-5.29). Test compounds showed good ADMET properties and similarity with respect to standard drugs. Molecular docking studies and in silico ADMET screening of new chalcones and their benzotriazole derivatives could be used as inhibitors of lanosterol α-demethylase (4WMZ) and DNA gyrase topoisomerase B (1KZN). Additional in-vitro and in-vivo research could confirm its potential as antimicrobials.