Modified D-Glucofuranoses as New Black Fungus Protease Inhibitors: Computational Screening, Docking, Dynamics, and QSAR Study

Abstract

Notable antimicrobial functionality were found with different sugar esters which were also reported to inhibit the multidrug resistant pathogens along with promising antimicrobial efficacy, and drug-likeness properties. Recent black fungus outbreak, especially in India, along with COVID-19 surmounted the death toll and worsened the conditions severely due to lack of appropriate drugs. Hence, several glucofuranose type esters 4-8 were screened against black fungus related protein (2WTP). These molecules, optimized by DFT, showed good chemical and biological reactivity values especially with pathogens along with satisfactory ADMET profiles. With the good in vitro antifungal activities these compounds were subjected for molecular docking against protein of mucormycosis’s pathogens, known as black fungus, followed by calculation of inhibition constant, binding energy, and molecular dynamics of the protein–ligand complex. Also, logpIC50 or pIC50 was calculated regarding the data for QSAR study. The molecular docking showed that 5-8 had good binding affinity (>-6.50 kcal/mol) while 7 (-8.00 kcal/mol) and 8 (-8.20 kcal/mol) possessed excellent binding affinity. The inhibition constant and binding energy of the compounds were found very lower among others with stable complexes in 5000 ns in molecular dynamics. Considering all the results, sugar ester 7 and 8 are found to have promising drug properties.