Novel Galactopyranoside Esters: Synthesis, Mechanism, In Vitro Antimicrobial Evaluation and Molecular Docking Studies
Priyanka Matin,
Umme Hanee,
Muhammad Shaiful Alam,
Jae Eon Jeong,
Mohammed Mahbubul Matin,
Md. Rezaur Rahman,
Shafi Mahmud,
Mohammed Merae Alshahrani,
Bonglee Kim
Affiliations
Priyanka Matin
Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh
Umme Hanee
Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh
Muhammad Shaiful Alam
Department of Pharmacy, University of Science and Technology Chittagong, Chittagong 4202, Bangladesh
Jae Eon Jeong
Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
Mohammed Mahbubul Matin
Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh
Md. Rezaur Rahman
Department of Chemical Engineering and Energy Sustainability, Faculty of Engineering, Universiti Malaysia Sarawak, Kota Samarahan 94300, Malaysia
Shafi Mahmud
Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, The Shine-Dalgarno Centre for RNA Innovation, The Australian National University, Canberra, ACT 2601, Australia
Mohammed Merae Alshahrani
Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia
Bonglee Kim
Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
One-step direct unimolar valeroylation of methyl α-D-galactopyranoside (MDG) mainly furnished the corresponding 6-O-valeroate. However, DMAP catalyzed a similar reaction that produced 2,6-di-O-valeroate and 6-O-valeroate, with the reactivity sequence as 6-OH > 2-OH > 3-OH,4-OH. To obtain novel antimicrobial agents, 6-O- and 2,6-di-O-valeroate were converted into several 2,3,4-tri-O- and 3,4-di-O-acyl esters, respectively, with other acylating agents in good yields. The PASS activity spectra along with in vitro antimicrobial evaluation clearly indicated that these MDG esters had better antifungal activities than antibacterial agents. To rationalize higher antifungal potentiality, molecular docking was conducted with sterol 14α-demethylase (PDB ID: 4UYL, Aspergillus fumigatus), which clearly supported the in vitro antifungal results. In particular, MDG ester 7–12 showed higher binding energy than the antifungal drug, fluconazole. Additionally, these compounds were found to have more promising binding energy with the SARS-CoV-2 main protease (6LU7) than tetracycline, fluconazole, and native inhibitor N3. Detailed investigation of Ki values, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and the drug-likeness profile indicated that most of these compounds satisfy the drug-likeness evaluation, bioavailability, and safety tests, and hence, these synthetic novel MDG esters could be new antifungal and antiviral drugs.
