Synthesis, spectroscopic characterization, molecular docking, and ADMET studies of mannopyranoside esters as antimicrobial agents

• Published in: Journal of molecular structure 2020-12, Vol.1222, p.128821, Article 128821
• Main Authors: Matin, Mohammed M., Hasan, Md. S., Uzzaman, Monir, Bhuiyan, Md. Mosharef H., Kibria, Sayed M., Hossain, Md. E., Roshid, Mohammad H.O.
• Format: Article
• Language: English
• Subjects: ADMET; Antimicrobial activity; Hartree-Fock method; Methyl α-d-mannopyranoside (MDM); Molecular docking; PASS predication
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2020.128821

Regioselective unimolar one-step hexanoylation of methyl α-d-mannopyranoside (MDM) under controlled conditions furnished the 6-O-hexanoate and indicated the regioselectivity at C-6 position. To develop mannopyranoside based potential antimicrobial sugar esters (SEs), 6-O-hexanoate was further converted into five newer 2,3,4-tri-O-acyl esters reasonably in good yields. Both prediction of activity spectra for substances (PASS) and in vitro antimicrobial evaluation established these SEs as better antifungal agents than as antibacterials. Quantum chemical study has been performed to calculate the thermodynamic, molecular orbital and electrostatic potential properties. Molecular docking and nonbonding interactions have been performed against lanosterol 14α-demethylase (CYP51A1), A. flavus (1R51), and E. coli (4XO8) to search the binding affinity and interactions of MDM esters with the receptor proteins. ADMET prediction also performed to evaluate the absorption, metabolism, and toxic properties of SEs. Structure activity relationship (SAR) study along with in vitro, and in silico results indicated that amongst the acyl chains, caproic chain (C6) in combination with acetic (C2), caprylic (C8) or lauric (C12) chains were found the most promising against fungal pathogens. [Display omitted] •Controlled hexanoylation showed regioselectivity at C-6 OH position of methyl α-d-mannopyranoside (MDM).•6-O-Hexanoate was converted into five 2,3,4-tri-O-acyl esters with high yields.•MDM derived SEs are more effective against fungal pathogens.•The most promising antifungal property was found for caproic chain (C6) in combination with acetic (C2), caprylic (C8) or lauric (C12) chains.