Synthesis, antimicrobial evaluation, docking and dynamics investigation of novel stearoyl mannopyranosides

Abstract

The exploration of acylated monosaccharide derivatives, particularly those derived from mannose, stands as a pivotal endeavor with multifaceted synthetic applications in both the realms of medicine and industry. Given the escalating challenges posed by drug resistance in antifungal and antibacterial treatments, the imperative for innovative therapeutic agents becomes increasingly pronounced. In response to this critical need, several novel mannopyranoside stearate esters have been synthesized. Direct unimolar stearoylation of methyl α-d-mannopyranoside (1) at room temperature showed selectivity at C-6 primary position and furnished 6-O-stearoyl-α-d-mannopyranoside 2 in 61 % yield. The newly synthesized stearoate 2 was further modified into several acyl esters for developing some novel biologically active mannopyranoside esters. Furthermore, the synthesized stearoyl esters were employed for prediction of activity spectra for substances (PASS) and in vitro antimicrobial assay. It was found that the experimental esters were more potent against fungal pathogens than that of bacterial organisms. Moreover, advocating for the antifungal efficacy, molecular docking investigations were conducted on the synthesized stearates, revealing enhanced binding affinities with lanosterol 14α-demethylase (3LD6) protein. Notably, stearates 2 (-7.7 kcal/mol) and 3 (-7.9 kcal/mol) demonstrated higher binding affinities with the model protein. Molecular dynamic simulation studies further revealed significant interactions for compounds 2 and 3, suggesting strong potential for these synthesized stearates to be developed as non-azole-type biodegradable antifungal agents.

Keywords

• D-mannopyranoside
• Acyl esters
• Antimicrobial assay
• PASS analysis