Abstract
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 IC50 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.
Highlights
Carbohydrates are important molecules in nature that play a variety of roles in biological processes
These MGP analogs were subjected to antimicrobial testing and geometrical optimization to determine the mode of their antimicrobial behavior
Because all of the designed MGP analogs have a smaller highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap than MGP, the modified compounds are more reactive than the parent drug
Summary
Carbohydrates are important molecules in nature that play a variety of roles in biological processes. Carbohydrates have been a very attractive topic for scientists due to their immense importance in biological systems, including viral and bacterial infections, cell growth and proliferation, cell-cell communication, and immune response [1,2] They are the source of the metabolic energy supply and the fine-tuning of cell-cell interactions and other crucial processes [3,4]. It was found from the literature survey that a large number of biologically active compounds possess aromatic, heteroaromatic, and acyl substituents [5,6,7,8,9,10,11,12]. This study aimed to investigate the inhibitory effect of several synthesized MGP analogs against novel coronavirus through synthetic, spectral, anticancer and several in silico and computational approaches, namely DFT analysis, molecular docking, molecular dynamics, and targeting SARS-CoV-2 main protease as a prospective receptor
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