Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs
Md. Ruhul Amin,
Farhana Yasmin,
Mohammed Anowar Hosen,
Sujan Dey,
Shafi Mahmud,
Md. Abu Saleh,
Talha Bin Emran,
Imtiaj Hasan,
Yuki Fujii,
Masao Yamada,
Yasuhiro Ozeki,
Sarkar Mohammad Abe Kawsar
Affiliations
Md. Ruhul Amin
Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh
Farhana Yasmin
Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh
Mohammed Anowar Hosen
Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh
Sujan Dey
Department of Microbiology, Faculty of Biological Science, University of Chittagong, Chittagong 4331, Bangladesh
Shafi Mahmud
Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh
Md. Abu Saleh
Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh
Talha Bin Emran
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
Imtiaj Hasan
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh
Yuki Fujii
School of Pharmaceutical Sciences, Nagasaki International University, 2825-7, Huis Ten Bosch-cho, Sasebo, Nagasaki 859-3298, Japan
Masao Yamada
School of Sciences, Yokohama City University, 22-2, Seto, Kanazawa-ku, Yokohama 236-0027, Japan
Yasuhiro Ozeki
School of Sciences, Yokohama City University, 22-2, Seto, Kanazawa-ku, Yokohama 236-0027, Japan
Sarkar Mohammad Abe Kawsar
Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh
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.
