In vitro antimicrobial, anticancer evaluation, and in silico studies of mannopyranoside analogs against bacterial and fungal proteins: Acylation leads to improved antimicrobial activity

Carbohydrate analogs are an important, well-established class of clinically useful medicinal agents that exhibit potent antimicrobial activity. Thus, we explored the various therapeutic potential of methyl alpha-D-mannopyranoside (M alpha DM) analogs, including their ability to synthesize and assess their antibacterial, antifungal, and anticancer properties; additionally, molecular docking, molecular dynamics simulation, and ADMET analysis were performed. The structure of the synthesized M alpha DM analogs was ascertained by spectroscopic techniques and physicochemical and elemental analysis. In vitro antimicrobial activity was assessed and revealed significant inhibitory effects, particularly against gram-negative bacteria along with the prediction of activity spectra for substances (PASS). Concurrently, M alpha DM analogs showed good results against antifungal pathogens and exhibited promising anticancer effects in vitro, demonstrating dose-dependent cytotoxicity against Ehrlich ascites carcinoma (EAC) cancer cells while sparing normal cells from compound 5, with an IC50 of 4511.65 mu g/mL according to the MTT colorimetric assay. A structure-activity relationship (SAR) study revealed that hexose combined with the acyl chains of decanoyl (C-10) and benzenesulfonyl (C6H5SO2-) had synergistic effects on the bacteria and fungi that were examined. Molecular docking was performed against the Escherichia coli (6KZV) and Candida albicans (1EAG) proteins to acquire insights into the molecular interactions underlying the observed biological activities. The docking results were further supported by 100 ns molecular dynamics simulations, which provided a dynamic view of the stability and flexibility of complexes involving M alpha DM and its targets. In addition, ADMET analysis was used to evaluate the toxicological and pharmacokinetic profiles. Owing to their promising drug-like properties, these M alpha DM analogs exhibit potential as prospective therapeutic candidates for future development.