Discovery of New Boswellic Acid Hybrid 1<i>H</i>-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies
A series of 24 new 1<i>H</i>-1,2,3-triazole hybrids of 3-<i>O</i>-acetyl-11-keto-β-boswellic acid (β-AKBA (<b>1</b>)) and 11-keto-β-boswellic acid (β-KBA (<b>2</b>)) was designed and synthesized by employing “click” chemistry in a highly efficient mann...
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MDPI AG
2023-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/2/229 |
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| author | Najeeb Ur Rehman Saeed Ullah Tanveer Alam Sobia Ahsan Halim Tapan Kumar Mohanta Ajmal Khan Muhammad U. Anwar René Csuk Satya Kumar Avula Ahmed Al-Harrasi |
| author_facet | Najeeb Ur Rehman Saeed Ullah Tanveer Alam Sobia Ahsan Halim Tapan Kumar Mohanta Ajmal Khan Muhammad U. Anwar René Csuk Satya Kumar Avula Ahmed Al-Harrasi |
| author_sort | Najeeb Ur Rehman |
| collection | DOAJ |
| description | A series of 24 new 1<i>H</i>-1,2,3-triazole hybrids of 3-<i>O</i>-acetyl-11-keto-β-boswellic acid (β-AKBA (<b>1</b>)) and 11-keto-β-boswellic acid (β-KBA (<b>2</b>)) was designed and synthesized by employing “click” chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between β-AKBA-propargyl ester intermediate <b>3</b> or β-KBA-propargyl ester intermediate <b>4</b> with substituted aromatic azides <b>5a–5k</b> in the presence of copper iodide (CuI) and Hünig’s base furnished the desired products—1<i>H</i>-1,2,3-triazole hybrids of β-AKBA (<b>6a–6k</b>) and β-KBA (<b>7a–7k</b>)—in high yields. All new synthesized compounds were characterized by <sup>1</sup>H-, <sup>13</sup>C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their α-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the α-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC<sub>50</sub> values ranging from 0.22 to 5.32 µM. Among all the compounds, <b>6f</b>, <b>7h</b>, <b>6j</b>, <b>6h</b>, <b>6g</b>, <b>6c</b>, <b>6k</b>, <b>7g</b>, and <b>7k</b> exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds <b>1</b> and <b>2</b>, as well as standard acarbose. Kinetic studies of compounds <b>6g</b> and <b>7h</b> exhibited competitive and mixed types of inhibition, with ki values of 0.84 ± 0.007 and 1.18 ± 0.0012 µM, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with α-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of α-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1<i>H</i>-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton. |
| first_indexed | 2024-03-11T08:17:32Z |
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| last_indexed | 2024-03-11T08:17:32Z |
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| spelling | doaj.art-037896da8e214de3bfe28471398946f22023-11-16T22:36:47ZengMDPI AGPharmaceuticals1424-82472023-02-0116222910.3390/ph16020229Discovery of New Boswellic Acid Hybrid 1<i>H</i>-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico StudiesNajeeb Ur Rehman0Saeed Ullah1Tanveer Alam2Sobia Ahsan Halim3Tapan Kumar Mohanta4Ajmal Khan5Muhammad U. Anwar6René Csuk7Satya Kumar Avula8Ahmed Al-Harrasi9Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanOrganic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), GermanyNatural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, OmanA series of 24 new 1<i>H</i>-1,2,3-triazole hybrids of 3-<i>O</i>-acetyl-11-keto-β-boswellic acid (β-AKBA (<b>1</b>)) and 11-keto-β-boswellic acid (β-KBA (<b>2</b>)) was designed and synthesized by employing “click” chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between β-AKBA-propargyl ester intermediate <b>3</b> or β-KBA-propargyl ester intermediate <b>4</b> with substituted aromatic azides <b>5a–5k</b> in the presence of copper iodide (CuI) and Hünig’s base furnished the desired products—1<i>H</i>-1,2,3-triazole hybrids of β-AKBA (<b>6a–6k</b>) and β-KBA (<b>7a–7k</b>)—in high yields. All new synthesized compounds were characterized by <sup>1</sup>H-, <sup>13</sup>C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their α-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the α-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC<sub>50</sub> values ranging from 0.22 to 5.32 µM. Among all the compounds, <b>6f</b>, <b>7h</b>, <b>6j</b>, <b>6h</b>, <b>6g</b>, <b>6c</b>, <b>6k</b>, <b>7g</b>, and <b>7k</b> exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds <b>1</b> and <b>2</b>, as well as standard acarbose. Kinetic studies of compounds <b>6g</b> and <b>7h</b> exhibited competitive and mixed types of inhibition, with ki values of 0.84 ± 0.007 and 1.18 ± 0.0012 µM, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with α-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of α-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1<i>H</i>-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton.https://www.mdpi.com/1424-8247/16/2/2293-<i>O</i>-acetyl-11-keto-β-boswellic acid (AKBA)11-keto-β-boswellic acid (KBA)1<i>H</i>-1,2,3-triazole hybridsclick chemistryα-glucosidase inhibitorsmolecular docking studies |
| spellingShingle | Najeeb Ur Rehman Saeed Ullah Tanveer Alam Sobia Ahsan Halim Tapan Kumar Mohanta Ajmal Khan Muhammad U. Anwar René Csuk Satya Kumar Avula Ahmed Al-Harrasi Discovery of New Boswellic Acid Hybrid 1<i>H</i>-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies Pharmaceuticals 3-<i>O</i>-acetyl-11-keto-β-boswellic acid (AKBA) 11-keto-β-boswellic acid (KBA) 1<i>H</i>-1,2,3-triazole hybrids click chemistry α-glucosidase inhibitors molecular docking studies |
| title | Discovery of New Boswellic Acid Hybrid 1<i>H</i>-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies |
| title_full | Discovery of New Boswellic Acid Hybrid 1<i>H</i>-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies |
| title_fullStr | Discovery of New Boswellic Acid Hybrid 1<i>H</i>-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies |
| title_full_unstemmed | Discovery of New Boswellic Acid Hybrid 1<i>H</i>-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies |
| title_short | Discovery of New Boswellic Acid Hybrid 1<i>H</i>-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies |
| title_sort | discovery of new boswellic acid hybrid 1 i h i 1 2 3 triazoles for diabetic management in vitro and in silico studies |
| topic | 3-<i>O</i>-acetyl-11-keto-β-boswellic acid (AKBA) 11-keto-β-boswellic acid (KBA) 1<i>H</i>-1,2,3-triazole hybrids click chemistry α-glucosidase inhibitors molecular docking studies |
| url | https://www.mdpi.com/1424-8247/16/2/229 |
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