Macromolecules: Synthesis, antimicrobial, POM analysis and computational approaches of some glucoside derivatives bearing acyl moieties

Mohammad R Kayes; Supriyo Saha; Mohammed M Alanazi; Yasuhiro Ozeki; Dilipkumar Pal; Taibi B Hadda; Abdelkhaleq Legssyer; Sarkar M A Kawsar

doi:10.1016/j.jsps.2023.101804

Macromolecules: Synthesis, antimicrobial, POM analysis and computational approaches of some glucoside derivatives bearing acyl moieties

Saudi Pharm J. 2023 Nov;31(11):101804. doi: 10.1016/j.jsps.2023.101804. Epub 2023 Oct 2.

Authors

Mohammad R Kayes¹, Supriyo Saha², Mohammed M Alanazi³, Yasuhiro Ozeki⁴, Dilipkumar Pal⁵, Taibi B Hadda⁶, Abdelkhaleq Legssyer⁶, Sarkar M A Kawsar¹

Affiliations

¹ Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh.
² Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, Uttarakhand 248007, India.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
⁴ School of Sciences, Yokohama City University, 22-2, Seto, Kanazawa-Ku, Yokohama 236-0027, Japan.
⁵ Department of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), C.G, 495009 Bilaspur, India.
⁶ BBEH and LACE Laboratories of Applied Chemistry & Environment, Faculty of Sciences, Mohammed Premier University, MB 524, 60000 Oujda, Morocco.

Abstract

Macromolecules i.e., carbohydrate derivatives are crucial to biochemical and medical research. Herein, we designed and synthesized eight methyl α-D-glucopyranoside (MGP) derivatives (2-8) in good yields following the regioselective direct acylation method. The structural configurations of the synthesized MGP derivatives were analyzed and verified using multiple physicochemical and spectroscopic techniques. Antimicrobial experiments revealed that almost all derivatives demonstrated noticeable antifungal and antibacterial efficacy. The synthesized derivatives showed minimum inhibitory concentration (MIC) values ranging from 0.75 µg/mL to 1.50 µg/mL and minimum bactericidal concentrations (MBCs) ranging from 8.00 µg/mL to 16.00 µg/mL. Compound 6 inhibited Ehrlich ascites carcinoma (EAC) cell proliferation by 10.36% with an IC50 of 2602.23 μg/mL in the MTT colorimetric assay. The obtained results were further rationalized by docking analysis of the synthesized derivatives against 4URO and 4XE3 receptors to explore the binding affinities and nonbonding interactions of MGP derivatives with target proteins. Compound 6 demonstrated the potential to bind with the target with the highest binding energy. In a stimulating environment, a molecular dynamics study showed that MGP derivatives have a stable conformation and binding pattern. The MGP derivatives were examined using POM (Petra/Osiris/Molinspiration) bioinformatics, and as a result, these derivatives showed good toxicity, bioavailability, and pharmacokinetics. Various antifungal/antiviral pharmacophore (O^δ-, O'^δ-) sites were identified by using POM investigations, and compound 6 was further tested against other pathogenic fungi and viruses, such as Micron and Delta mutants of SARS-CoV-2.

Keywords: Antimicrobial; Antiproliferative; Computational approaches, POM; Glucoside; Molecular docking/dynamics.