Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies
AbstractMulti-target inhibitors represent useful anticancer agents with superior therapeutic attributes. Here in, two novel series of benzimidazole-triazole hybrids were designed, synthesised as multi-target EGFR, VEGFR-2 and Topo II inhibitors, and evaluated for anticancer activity. Compounds 5a an...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2166037 |
| _version_ | 1797400922226163712 |
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| author | Dina I. A. Othman Abdelrahman Hamdi Samar S. Tawfik Abdullah A. Elgazar Amany S. Mostafa |
| author_facet | Dina I. A. Othman Abdelrahman Hamdi Samar S. Tawfik Abdullah A. Elgazar Amany S. Mostafa |
| author_sort | Dina I. A. Othman |
| collection | DOAJ |
| description | AbstractMulti-target inhibitors represent useful anticancer agents with superior therapeutic attributes. Here in, two novel series of benzimidazole-triazole hybrids were designed, synthesised as multi-target EGFR, VEGFR-2 and Topo II inhibitors, and evaluated for anticancer activity. Compounds 5a and 6g were the most potent analogues against four cancer cell lines, HepG-2, HCT-116, MCF-7 and HeLa, and were further evaluated for EGFR, VEGFR-2, and Topo II inhibition. Compound 5a was especially good inhibitor for EGFR (IC50 = 0.086 µM) compared to Gefitinib (IC50 = 0.052 µM), moderate VEGFR-2 inhibitor (IC50 = 0.107 µM) compared to Sorafenib (IC50 = 0.0482 µM), and stronger Topo II inhibitor (IC50 = 2.52 µM) than Doxorubicin (IC50 = 3.62 µM). Compound 6g exhibited moderate EGFR and VEGFR-2 inhibition and weaker Topo II inhibition. DNA binding assay, cell cycle analysis, apoptotic induction, molecular docking, and physicochemical studies were additionally implemented to explore the plausible mechanism of the active compounds. |
| first_indexed | 2024-03-09T02:02:28Z |
| format | Article |
| id | doaj.art-19091a4a39dc48c488a42b98d4cbbb79 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:02:28Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-19091a4a39dc48c488a42b98d4cbbb792023-12-08T03:24:21ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2166037Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studiesDina I. A. Othman0Abdelrahman Hamdi1Samar S. Tawfik2Abdullah A. Elgazar3Amany S. Mostafa4Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptAbstractMulti-target inhibitors represent useful anticancer agents with superior therapeutic attributes. Here in, two novel series of benzimidazole-triazole hybrids were designed, synthesised as multi-target EGFR, VEGFR-2 and Topo II inhibitors, and evaluated for anticancer activity. Compounds 5a and 6g were the most potent analogues against four cancer cell lines, HepG-2, HCT-116, MCF-7 and HeLa, and were further evaluated for EGFR, VEGFR-2, and Topo II inhibition. Compound 5a was especially good inhibitor for EGFR (IC50 = 0.086 µM) compared to Gefitinib (IC50 = 0.052 µM), moderate VEGFR-2 inhibitor (IC50 = 0.107 µM) compared to Sorafenib (IC50 = 0.0482 µM), and stronger Topo II inhibitor (IC50 = 2.52 µM) than Doxorubicin (IC50 = 3.62 µM). Compound 6g exhibited moderate EGFR and VEGFR-2 inhibition and weaker Topo II inhibition. DNA binding assay, cell cycle analysis, apoptotic induction, molecular docking, and physicochemical studies were additionally implemented to explore the plausible mechanism of the active compounds.https://www.tandfonline.com/doi/10.1080/14756366.2023.2166037Benzimidazole123-triazole hybridsanticancerEGFRVEGFR-2Topo II |
| spellingShingle | Dina I. A. Othman Abdelrahman Hamdi Samar S. Tawfik Abdullah A. Elgazar Amany S. Mostafa Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies Journal of Enzyme Inhibition and Medicinal Chemistry Benzimidazole 123-triazole hybrids anticancer EGFR VEGFR-2 Topo II |
| title | Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies |
| title_full | Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies |
| title_fullStr | Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies |
| title_full_unstemmed | Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies |
| title_short | Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies |
| title_sort | identification of new benzimidazole triazole hybrids as anticancer agents multi target recognition in vitro and in silico studies |
| topic | Benzimidazole 123-triazole hybrids anticancer EGFR VEGFR-2 Topo II |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2166037 |
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