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

Md Ahad Hossain; Shahin Sultana; Mohammed M Alanazi; Hanine Hadni; Ajmal R Bhat; Imtiaj Hasan; Sarkar M A Kawsar

doi:10.1016/j.jsps.2024.102093

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

Saudi Pharm J. 2024 Jun;32(6):102093. doi: 10.1016/j.jsps.2024.102093. Epub 2024 Apr 30.

Authors

Md Ahad Hossain¹, Shahin Sultana¹, Mohammed M Alanazi², Hanine Hadni³, Ajmal R Bhat⁴, Imtiaj Hasan⁵, Sarkar M A Kawsar¹

Affiliations

¹ Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh.
² Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
³ LIMAS, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
⁴ Department of Chemistry, RTM Nagpur University, Nagpur 440033, India.
⁵ Department of Biochemistry and Molecular Biology, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh.

Abstract

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 α-D-mannopyranoside (MαDM) 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 MαDM 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, MαDM 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 µg/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 MαDM and its targets. In addition, ADMET analysis was used to evaluate the toxicological and pharmacokinetic profiles. Owing to their promising drug-like properties, these MαDM analogs exhibit potential as prospective therapeutic candidates for future development.

Keywords: ADMET; Anticancer; Antimicrobial; MD; Mannopyranoside (MαDM); Molecular docking.