Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations
A library of novel imidazole-1,2,3-triazole hybrids were designed and synthesized based on the hybrid pharmacophore approach. Therefore, copper(I)catalyzed click reaction of thiopropargylated-imidazole 2 with several organoazides yielded two sets of imidazole-1,2,3-triazole hybrids carrying differen...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1162 |
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| author | Fawzia Al-blewi Salma Akram Shaikh Arshi Naqvi Faizah Aljohani Mohamed Reda Aouad Saleh Ihmaid Nadjet Rezki |
| author_facet | Fawzia Al-blewi Salma Akram Shaikh Arshi Naqvi Faizah Aljohani Mohamed Reda Aouad Saleh Ihmaid Nadjet Rezki |
| author_sort | Fawzia Al-blewi |
| collection | DOAJ |
| description | A library of novel imidazole-1,2,3-triazole hybrids were designed and synthesized based on the hybrid pharmacophore approach. Therefore, copper(I)catalyzed click reaction of thiopropargylated-imidazole 2 with several organoazides yielded two sets of imidazole-1,2,3-triazole hybrids carrying different un/functionalized alkyl/aryl side chains <b>4a</b>–<b>k</b> and <b>6a</b>–<b>e</b>. After full spectroscopic characterization using different spectral techniques (IR, <sup>1</sup>H, <sup>13</sup>C NMR) and elemental analyses, the resulted adducts were screened for their anticancer activity against four cancer cell lines (Caco-2, HCT-116, HeLa, and MCF-7) by the MTT assay and showed significant activity. In-silico molecular docking study was also investigated on one of the prominent cancer target receptors, i.e., glycogen synthase kinase-3β (GSK-3β), revealing a good binding interaction with our potent compound, <b>4k</b> and was in agreement with the in vitro cytotoxic results. In addition, the ADMET profile was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes. Finally, this research design and synthesis offered click chemistry products with interesting biological motifs mainly 1,2,3 triazoles linked to phenyl imidazole as promising candidates for further investigation as anticancer drugs. |
| first_indexed | 2024-03-09T03:46:39Z |
| format | Article |
| id | doaj.art-a8be48d7879944be9a01fda16855b74e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:46:39Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a8be48d7879944be9a01fda16855b74e2023-12-03T14:34:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223116210.3390/ijms22031162Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking InvestigationsFawzia Al-blewi0Salma Akram Shaikh1Arshi Naqvi2Faizah Aljohani3Mohamed Reda Aouad4Saleh Ihmaid5Nadjet Rezki6Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaPharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaA library of novel imidazole-1,2,3-triazole hybrids were designed and synthesized based on the hybrid pharmacophore approach. Therefore, copper(I)catalyzed click reaction of thiopropargylated-imidazole 2 with several organoazides yielded two sets of imidazole-1,2,3-triazole hybrids carrying different un/functionalized alkyl/aryl side chains <b>4a</b>–<b>k</b> and <b>6a</b>–<b>e</b>. After full spectroscopic characterization using different spectral techniques (IR, <sup>1</sup>H, <sup>13</sup>C NMR) and elemental analyses, the resulted adducts were screened for their anticancer activity against four cancer cell lines (Caco-2, HCT-116, HeLa, and MCF-7) by the MTT assay and showed significant activity. In-silico molecular docking study was also investigated on one of the prominent cancer target receptors, i.e., glycogen synthase kinase-3β (GSK-3β), revealing a good binding interaction with our potent compound, <b>4k</b> and was in agreement with the in vitro cytotoxic results. In addition, the ADMET profile was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes. Finally, this research design and synthesis offered click chemistry products with interesting biological motifs mainly 1,2,3 triazoles linked to phenyl imidazole as promising candidates for further investigation as anticancer drugs.https://www.mdpi.com/1422-0067/22/3/11621,2,3-triazoleimidazoleclick synthesisanticancer activitydocking study |
| spellingShingle | Fawzia Al-blewi Salma Akram Shaikh Arshi Naqvi Faizah Aljohani Mohamed Reda Aouad Saleh Ihmaid Nadjet Rezki Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations International Journal of Molecular Sciences 1,2,3-triazole imidazole click synthesis anticancer activity docking study |
| title | Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations |
| title_full | Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations |
| title_fullStr | Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations |
| title_full_unstemmed | Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations |
| title_short | Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations |
| title_sort | design and synthesis of novel imidazole derivatives possessing triazole pharmacophore with potent anticancer activity and in silico admet with gsk 3β molecular docking investigations |
| topic | 1,2,3-triazole imidazole click synthesis anticancer activity docking study |
| url | https://www.mdpi.com/1422-0067/22/3/1162 |
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