A series of methyl β-D-galactopyranoside (MGP, 1 ) analogs were selectively acylated with cinnamoyl chloride in anhydrous N , N -dimethylformamide/triethylamine to yield 6- O -substitution products, which was subsequently converted into 2,3,4-tri- O -acyl analogs with different acyl halides. Analysis of the physicochemical, elemental, and spectroscopic data of these analogs revealed their chemical structures. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) showed promising antifungal functionality comparing to their antibacterial activities. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests were conducted for four compounds ( 4 , 5 , 6 , and 9 ) based on their activity. MTT assay showed low antiproliferative activity of compound 9 against Ehrlich’s ascites carcinoma (EAC) cells with an IC 50 value of 2961.06 µg/mL. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties whereas molecular docking identified potential inhibitors of the SARS-CoV-2 main protease (6Y84). A 150-ns molecular dynamics simulation study revealed the stable conformation and binding patterns in a stimulating environment. In-silico ADMET study suggested all the designed molecules to be non-carcinogenic, with low aquatic and non-aquatic toxicity. In summary, all these antimicrobial, anticancer and in silico studies revealed that newly synthesized MGP analogs possess promising antiviral activity, to serve as a therapeutic target for COVID-19.
【저자키워드】 molecular docking, molecular dynamics, synthesis, pharmacokinetic, Pass, methyl β-D-galactopyranoside, 【초록키워드】 COVID-19, Toxicity, protease, antiviral activity, in silico, Molecular dynamics simulation, Density functional theory, Bacteria, inhibitor, fungi, MBC, Concentration, structures, therapeutic target, chloride, Compound, activities, minimum, anticancer, FIVE, Cell, MTT, was used, conducted, suggested, thermodynamic, binding pattern, calculate, MGP, physicochemical, physicochemical property, the SARS-CoV-2, 【제목키워드】 prediction, antimicrobial, Simulation, dynamic,