MONOSACCHARIDE DERIVATIVES: SYNTHESIS, ANTIMICROBIAL, PASS, ANTIVIRAL AND MOLECULAR DOCKING STUDIES AGAINST SARS-COV-2 MPRO INHIBITORS

Several carbohydrate-based drugs are currently being used to treat a number of diseases in humans worldwide. Thus, our research group has focused on the synthesis of new methyl alpha-D-mannopyranoside (MDM) derivatives and their antimicrobial evaluation through computational studies. A series of MDM derivatives (2-6) were synthesized through facile regioselective acylation, using the direct method affording 6-O-(3-chlorobenzoyl) derivatives. This isolated 6-O-derivative was further transformed to 2,3,4-tri-O-acyl derivatives, bearing a wide variety of functionalities in a single molecular framework. The structures of the newly designed molecules were elucidated with the aid of IR, H-1 NMR, mass spectroscopy, and elemental analysis. The prediction of the activity spectra for the compounds (PASS) and their in vitro antimicrobial evaluation were performed, demonstrating them to be potential antimicrobial agents. The antimicrobial tests demonstrated that the compounds 3 and 5 were the most potent with the minimum inhibitory concentration (MIC) values, ranging from 0.312 +/- 0.01 to 1.25 +/- 0.03 mg/mL, and minimum bactericidal concentration (MBC) values, ranging from 0.625 +/- 0.02 to 2.50 +/- 0.05 mg/mL. A quantum chemical study was performed to calculate the thermodynamic, molecular orbital and electrostatic potential properties of the designed compounds. Molecular docking simulation was carried out against SARS-CoV-2 M-pro protein 7BQY and 6Y84 to investigate their binding energy and binding tactics with the viral protein, and better binding affinity than that of the parent drug was observed. Also, pharmacokinetic prediction revealed an improved drug-likeness profile for all MDM derivatives.