Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies
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...
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/3/986 |
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| author | Abul Fazal Muhammad Sanaullah Puja Devi Takbir Hossain Sulaiman Bin Sultan Mohammad Mohib Ullah Badhon Md. Emdad Hossain Jamal Uddin Md. Abdul Majed Patwary Mohsin Kazi Mohammed Mahbubul Matin |
| author_facet | Abul Fazal Muhammad Sanaullah Puja Devi Takbir Hossain Sulaiman Bin Sultan Mohammad Mohib Ullah Badhon Md. Emdad Hossain Jamal Uddin Md. Abdul Majed Patwary Mohsin Kazi Mohammed Mahbubul Matin |
| author_sort | Abul Fazal Muhammad Sanaullah |
| collection | DOAJ |
| description | 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-<i>O</i>-stearoylation of methyl α-<span style="font-variant: small-caps;">l</span>-rhamnopyranoside (<b>3</b>) produced a mixture of 2,3-di-<i>O</i>- (<b>4</b>) and 3,4-di-<i>O</i>-stearates (<b>5</b>) (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-<i>O</i>-stearates <b>4</b> and <b>5</b> were converted into six 4-<i>O</i>- and 2-<i>O</i>-esters <b>6</b>–<b>11</b>, which were fully characterized by FT-IR, <sup>1</sup>H, and <sup>13</sup>C NMR spectral techniques. In vitro antimicrobial assays revealed that fully esterified rhamnopyranosides <b>6</b>–<b>11</b> 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-<i>O</i>-stearate (compound <b>6</b>) showed better antifungal functionality against <i>F. equiseti</i> and <i>A. flavus</i>, which were found to be better than standard antibiotics. To validate the better antifungal results, molecular docking of the rhamnose esters <b>4</b>–<b>11</b> was performed with lanosterol 14α-demethylase (PDB ID: 3LD6), including the standard antifungal antibiotics ketoconazole and fluconazole. In this instance, the binding affinities of <b>10</b> (−7.6 kcal/mol), <b>9</b> (−7.5 kcal/mol), and <b>7</b> (−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. |
| first_indexed | 2024-03-11T09:34:02Z |
| format | Article |
| id | doaj.art-1be9a03ee3f742739f2d942f0164dead |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
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| last_indexed | 2024-03-11T09:34:02Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-1be9a03ee3f742739f2d942f0164dead2023-11-16T17:25:59ZengMDPI AGMolecules1420-30492023-01-0128398610.3390/molecules28030986Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking StudiesAbul Fazal Muhammad Sanaullah0Puja Devi1Takbir Hossain2Sulaiman Bin Sultan3Mohammad Mohib Ullah Badhon4Md. Emdad Hossain5Jamal Uddin6Md. Abdul Majed Patwary7Mohsin Kazi8Mohammed Mahbubul Matin9Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, BangladeshBioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, BangladeshBioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, BangladeshBioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, BangladeshBioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, BangladeshWazed Miah Science Research Centre (WMSRC), Jahangirnagar University, Savar, Dhaka 1342, BangladeshCenter for Nanotechnology, Department of Natural Sciences, Coppin State University, Baltimore, MD 21216, USADepartment of Chemistry, Comilla University, Cumilla 3506, BangladeshDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaBioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, BangladeshThe 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-<i>O</i>-stearoylation of methyl α-<span style="font-variant: small-caps;">l</span>-rhamnopyranoside (<b>3</b>) produced a mixture of 2,3-di-<i>O</i>- (<b>4</b>) and 3,4-di-<i>O</i>-stearates (<b>5</b>) (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-<i>O</i>-stearates <b>4</b> and <b>5</b> were converted into six 4-<i>O</i>- and 2-<i>O</i>-esters <b>6</b>–<b>11</b>, which were fully characterized by FT-IR, <sup>1</sup>H, and <sup>13</sup>C NMR spectral techniques. In vitro antimicrobial assays revealed that fully esterified rhamnopyranosides <b>6</b>–<b>11</b> 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-<i>O</i>-stearate (compound <b>6</b>) showed better antifungal functionality against <i>F. equiseti</i> and <i>A. flavus</i>, which were found to be better than standard antibiotics. To validate the better antifungal results, molecular docking of the rhamnose esters <b>4</b>–<b>11</b> was performed with lanosterol 14α-demethylase (PDB ID: 3LD6), including the standard antifungal antibiotics ketoconazole and fluconazole. In this instance, the binding affinities of <b>10</b> (−7.6 kcal/mol), <b>9</b> (−7.5 kcal/mol), and <b>7</b> (−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.https://www.mdpi.com/1420-3049/28/3/986di-<i>O</i>-stearatein vitro testmethyl α-<span style="font-variant: small-caps">l</span>-rhamnopyranosidemolecular dockingregioselective acylationstructure-activity relationship |
| spellingShingle | Abul Fazal Muhammad Sanaullah Puja Devi Takbir Hossain Sulaiman Bin Sultan Mohammad Mohib Ullah Badhon Md. Emdad Hossain Jamal Uddin Md. Abdul Majed Patwary Mohsin Kazi Mohammed Mahbubul Matin Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies Molecules di-<i>O</i>-stearate in vitro test methyl α-<span style="font-variant: small-caps">l</span>-rhamnopyranoside molecular docking regioselective acylation structure-activity relationship |
| title | Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies |
| title_full | Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies |
| title_fullStr | Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies |
| title_full_unstemmed | Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies |
| title_short | Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies |
| title_sort | rhamnopyranoside based fatty acid esters as antimicrobials synthesis spectral characterization pass antimicrobial and molecular docking studies |
| topic | di-<i>O</i>-stearate in vitro test methyl α-<span style="font-variant: small-caps">l</span>-rhamnopyranoside molecular docking regioselective acylation structure-activity relationship |
| url | https://www.mdpi.com/1420-3049/28/3/986 |
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