Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies
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Published:2023-01-18
Issue:3
Volume:28
Page:986
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Sanaullah Abul Fazal Muhammad1ORCID, Devi Puja1, Hossain Takbir1ORCID, Sultan Sulaiman Bin1ORCID, Badhon Mohammad Mohib Ullah1, Hossain Md. Emdad2ORCID, Uddin Jamal3ORCID, Patwary Md. Abdul Majed4ORCID, Kazi Mohsin5ORCID, Matin Mohammed Mahbubul1ORCID
Affiliation:
1. Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh 2. Wazed Miah Science Research Centre (WMSRC), Jahangirnagar University, Savar, Dhaka 1342, Bangladesh 3. Center for Nanotechnology, Department of Natural Sciences, Coppin State University, Baltimore, MD 21216, USA 4. Department of Chemistry, Comilla University, Cumilla 3506, Bangladesh 5. Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
Abstract
The most widely used and accessible monosaccharides have a number of stereogenic centers that have been hydroxylated and are challenging to chemically separate. As a result, the task of regioselective derivatization of such structures is particularly difficult. Considering this fact and to get novel rhamnopyranoside-based esters, DMAP-catalyzed di-O-stearoylation of methyl α-l-rhamnopyranoside (3) produced a mixture of 2,3-di-O- (4) and 3,4-di-O-stearates (5) (ratio 2:3) indicating the reactivity of the hydroxylated stereogenic centers of rhamnopyranoside as 3-OH > 4-OH > 2-OH. To get novel biologically active rhamnose esters, di-O-stearates 4 and 5 were converted into six 4-O- and 2-O-esters 6–11, which were fully characterized by FT-IR, 1H, and 13C NMR spectral techniques. In vitro antimicrobial assays revealed that fully esterified rhamnopyranosides 6–11 with maximum lipophilic character showed better antifungal susceptibility than antibacterial activity. These experimental findings are similar to the results found from PASS analysis data. Furthermore, the pentanoyl derivative of 2,3-di-O-stearate (compound 6) showed better antifungal functionality against F. equiseti and A. flavus, which were found to be better than standard antibiotics. To validate the better antifungal results, molecular docking of the rhamnose esters 4–11 was performed with lanosterol 14α-demethylase (PDB ID: 3LD6), including the standard antifungal antibiotics ketoconazole and fluconazole. In this instance, the binding affinities of 10 (−7.6 kcal/mol), 9 (−7.5 kcal/mol), and 7 (−6.9 kcal/mol) were better and comparable to fluconazole (−7.3 kcal/mol), indicating the likelihood of their use as non-azole type antifungal drugs in the future.
Funder
Ministry of Science and Technology, Bangladesh King Saud University, Riyadh, Saudi Arabia
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference49 articles.
1. Sucrose fatty acid esters: Synthesis, emulsifying capacities, biological activities and structure-property profiles;Teng;Crit. Rev. Food Sci. Nutr.,2021 2. Selective sulfonylation of 4-C-hydroxymethyl-β-L-threo-pento-1,4-furanose: Synthesis of bicyclic diazasugars;Dhavale;Tetrahedron,2004 3. Ahmad, M.U., and Xu, X. (2015). Polar Lipids, Elsevier. 4. Novel mannopyranoside esters as sterol 14α-demethylase inhibitors: Synthesis, PASS predication, molecular docking, and pharmacokinetic studies;Matin;Carbohydr. Res.,2020 5. Snoch, W., Wnuk, D., Witko, T., Staroń, J., Bojarski, A.J., Jarek, E., Plou, F.J., and Guzik, M. (2021). In search of effective anticancer agents-Novel sugar esters based on polyhydroxyalkanoate monomers. Int. J. Mol. Sci., 22.
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