Synthesis, Characterizations, Anti-Diabetic and Molecular Modeling Approaches of Hybrid Indole-Oxadiazole Linked Thiazolidinone Derivatives
<b>Objective:</b> To synthesize hybrid compounds of indole and oxadiazole in search of highly effective anti-diabetic therapeutic agent. <b>Methods:</b> With the goal of advancing diabetes research, our group designed and synthesized a library of 15 compounds based on indole-...
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2024-10-01
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| author | Shoaib Khan Tayyiaba Iqbal Rafaqat Hussain Yousaf Khan Zanib Fiaz Fazal Rahim Hany W. Darwish |
| author_facet | Shoaib Khan Tayyiaba Iqbal Rafaqat Hussain Yousaf Khan Zanib Fiaz Fazal Rahim Hany W. Darwish |
| author_sort | Shoaib Khan |
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| description | <b>Objective:</b> To synthesize hybrid compounds of indole and oxadiazole in search of highly effective anti-diabetic therapeutic agent. <b>Methods:</b> With the goal of advancing diabetes research, our group designed and synthesized a library of 15 compounds based on indole-derived oxadiazole bearing varied substituted thiazolidinone via a multistep synthetic route. <sup>13</sup>C-NMR, <sup>1</sup>H-NMR and HREI-MS were applied for the characterization of all the synthesized compounds. Their biological inhibitory activity against diabetic enzymes, i.e., α-amylase and α-glucosidase was also determined. <b>Results:</b> Compound <b>7, 9 and 15 exhibited</b> excellent inhibition against α-amylase and α-glucosidase than the standard acarbose (IC<sub>50</sub> = 8.50 ± 0.10 µM for α-amylase and 9.30 ± 0.30 µM for α-glucosidase. To ensure the inhibitory actions of these potent analogs in molecular docking, an in silico approach was used. To determine the drug likeness of the reported analogs, an ADMET investigation was also carried out to explore the nature of the designed compounds if used as a drug. <b>Conclusion:</b> Fluoro-substituted analog 15 has stronger inhibition profile against both enzymes. All the potent compounds can be used as effective anti-diabetic therapeutic agents in future. |
| format | Article |
| id | doaj-art-74767b4406324fd2b5968f7d80c6611d |
| institution | OA Journals |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-10-01 |
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| spelling | doaj-art-74767b4406324fd2b5968f7d80c6611d2025-08-20T01:54:08ZengMDPI AGPharmaceuticals1424-82472024-10-011711142810.3390/ph17111428Synthesis, Characterizations, Anti-Diabetic and Molecular Modeling Approaches of Hybrid Indole-Oxadiazole Linked Thiazolidinone DerivativesShoaib Khan0Tayyiaba Iqbal1Rafaqat Hussain2Yousaf Khan3Zanib Fiaz4Fazal Rahim5Hany W. Darwish6Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, PakistanDepartment of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, PakistanCollege of Biology, Hunan University, Changsha 410082, ChinaDepartment of Chemistry, COMSATS University Islamabad, Islamabad 45550, PakistanDepartment of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, PakistanDepartment of Chemistry, Hazara University, Mansehra 21300, PakistanDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia<b>Objective:</b> To synthesize hybrid compounds of indole and oxadiazole in search of highly effective anti-diabetic therapeutic agent. <b>Methods:</b> With the goal of advancing diabetes research, our group designed and synthesized a library of 15 compounds based on indole-derived oxadiazole bearing varied substituted thiazolidinone via a multistep synthetic route. <sup>13</sup>C-NMR, <sup>1</sup>H-NMR and HREI-MS were applied for the characterization of all the synthesized compounds. Their biological inhibitory activity against diabetic enzymes, i.e., α-amylase and α-glucosidase was also determined. <b>Results:</b> Compound <b>7, 9 and 15 exhibited</b> excellent inhibition against α-amylase and α-glucosidase than the standard acarbose (IC<sub>50</sub> = 8.50 ± 0.10 µM for α-amylase and 9.30 ± 0.30 µM for α-glucosidase. To ensure the inhibitory actions of these potent analogs in molecular docking, an in silico approach was used. To determine the drug likeness of the reported analogs, an ADMET investigation was also carried out to explore the nature of the designed compounds if used as a drug. <b>Conclusion:</b> Fluoro-substituted analog 15 has stronger inhibition profile against both enzymes. All the potent compounds can be used as effective anti-diabetic therapeutic agents in future.https://www.mdpi.com/1424-8247/17/11/1428oxadiazolethiazolidinonediabetes miletusmolecular dockingADMET |
| spellingShingle | Shoaib Khan Tayyiaba Iqbal Rafaqat Hussain Yousaf Khan Zanib Fiaz Fazal Rahim Hany W. Darwish Synthesis, Characterizations, Anti-Diabetic and Molecular Modeling Approaches of Hybrid Indole-Oxadiazole Linked Thiazolidinone Derivatives Pharmaceuticals oxadiazole thiazolidinone diabetes miletus molecular docking ADMET |
| title | Synthesis, Characterizations, Anti-Diabetic and Molecular Modeling Approaches of Hybrid Indole-Oxadiazole Linked Thiazolidinone Derivatives |
| title_full | Synthesis, Characterizations, Anti-Diabetic and Molecular Modeling Approaches of Hybrid Indole-Oxadiazole Linked Thiazolidinone Derivatives |
| title_fullStr | Synthesis, Characterizations, Anti-Diabetic and Molecular Modeling Approaches of Hybrid Indole-Oxadiazole Linked Thiazolidinone Derivatives |
| title_full_unstemmed | Synthesis, Characterizations, Anti-Diabetic and Molecular Modeling Approaches of Hybrid Indole-Oxadiazole Linked Thiazolidinone Derivatives |
| title_short | Synthesis, Characterizations, Anti-Diabetic and Molecular Modeling Approaches of Hybrid Indole-Oxadiazole Linked Thiazolidinone Derivatives |
| title_sort | synthesis characterizations anti diabetic and molecular modeling approaches of hybrid indole oxadiazole linked thiazolidinone derivatives |
| topic | oxadiazole thiazolidinone diabetes miletus molecular docking ADMET |
| url | https://www.mdpi.com/1424-8247/17/11/1428 |
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