Potential antifungal activity of novel carbohydrate derivatives validated by POM, molecular docking and molecular dynamic simulations analyses

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ABSTRACT Our current study focuses on the molecular structures of the series of methyl 4,6-O-benzylidene-α-D-glucopyranoside 1–9 as potential antifungal agents to obtain more insight into the origin of their encouraging bioactivity. In vitro antimicrobial testing and the prediction of activity spectra for substances revealed that these carbohydrate derivatives have promising antifungal functionality compared to their antibacterial activities. In support of this finding, molecular docking was performed against lanosterol 14α-demethylase (CYP51A1) and Altemaria alternata (6LCC) by screening carbohydrate derivatives whereby significant binding affinities and non-bonding interactions have been observed against both microbial proteins. The majority of the derivatives studied here could bind near the critical catalytic residues. The molecular dynamics study has revealed that the complexes formed by these derivatives with the proteins lanosterol 14α-demethylase and Altemaria alternata can remain stable, both over time and in physiological conditions. The POM analysis shows the clear presence of an antifungal (O1δ-—O2δ-) pharmacophore site. ADMET and QSAR predictions were analysed to assess their pharmacokinetic and drug-likeness properties, showing promising results in silico. This work demonstrates that potential carbohydrate derivatives bind to fungal pathogens in an effort to circumvent their activities and open avenues for the development of newer antibiotics, which may target fungal pathogens.