Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agents
A new series of Pyrimidine (A, D and F) and quinazoline (B, C and E) analogues of 1,5-benzodiazepines were prepared via its nitrile-derived amidoximes in and nitrilium ions, respectively using one pot Domino reaction with DMAD in presence of DABCO catalyst and benzanilide in presence of Tf2O and 2-c...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | Journal of King Saud University: Science |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1018364719318579 |
| _version_ | 1818096825516687360 |
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| author | Apoorva Misra Dharma Kishore Ved Prakash Verma Sunil Dubey Subhash Chander Neha Gupta Sameer Bhagyawant Jaya Dwivedi Zeid A. Alothman Saikh Mohammad Wabaidur Swapnil Sharma |
| author_facet | Apoorva Misra Dharma Kishore Ved Prakash Verma Sunil Dubey Subhash Chander Neha Gupta Sameer Bhagyawant Jaya Dwivedi Zeid A. Alothman Saikh Mohammad Wabaidur Swapnil Sharma |
| author_sort | Apoorva Misra |
| collection | DOAJ |
| description | A new series of Pyrimidine (A, D and F) and quinazoline (B, C and E) analogues of 1,5-benzodiazepines were prepared via its nitrile-derived amidoximes in and nitrilium ions, respectively using one pot Domino reaction with DMAD in presence of DABCO catalyst and benzanilide in presence of Tf2O and 2-chloropyridine. The prepared molecules were examined for their biological property namely apoptotic and antiproliferative effects through cell cycle arrest using breast cancer cell line of human (MCF-7). Receptor-ligand interactions were studied on human epidermal evolution factor receptor (HER-2) with the help of molecular docking using Autodock 4.2.6 molecular modeling software. All the compounds demonstrated inhibitory effects on cell proliferation in a concentration dependent fashion (20–100 μg/mL). Notably, compound C exhibited highest inhibitory activity and caused inhibition of S and G2 phase in cell cycle arrest via caspase dependent apoptotic pathway in MCF-7 cells lines. Keywords: Pyrimidine, Quinazoline, 1,5-Benzodiazepines, Domino reaction, Anticancer agent |
| first_indexed | 2024-12-10T23:10:47Z |
| format | Article |
| id | doaj.art-efa9d90479b646f7b7664dbe43b744bf |
| institution | Directory Open Access Journal |
| issn | 1018-3647 |
| language | English |
| last_indexed | 2024-12-10T23:10:47Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of King Saud University: Science |
| spelling | doaj.art-efa9d90479b646f7b7664dbe43b744bf2022-12-22T01:29:58ZengElsevierJournal of King Saud University: Science1018-36472020-03-0132214861495Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agentsApoorva Misra0Dharma Kishore1Ved Prakash Verma2Sunil Dubey3Subhash Chander4Neha Gupta5Sameer Bhagyawant6Jaya Dwivedi7Zeid A. Alothman8Saikh Mohammad Wabaidur9Swapnil Sharma10Department of Chemistry, Banasthali Vidyapith, Banasthali 304022, Rajasthan, IndiaDepartment of Chemistry, Banasthali Vidyapith, Banasthali 304022, Rajasthan, IndiaDepartment of Chemistry, Banasthali Vidyapith, Banasthali 304022, Rajasthan, IndiaBirla Institute of Technology & Science, Pilani Campus, Pilani 333031, Rajasthan, IndiaSchool of Pharmacy, Maharaja Agrasen University, Solan, Himachal Pradesh 174103, IndiaSchool of Studies in Biotechnology, Jiwaji University, Gwalior 474011 Madhyapradesh, IndiaSchool of Studies in Biotechnology, Jiwaji University, Gwalior 474011 Madhyapradesh, IndiaDepartment of Chemistry, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India; Corresponding authors.Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacy, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India; Corresponding authors.A new series of Pyrimidine (A, D and F) and quinazoline (B, C and E) analogues of 1,5-benzodiazepines were prepared via its nitrile-derived amidoximes in and nitrilium ions, respectively using one pot Domino reaction with DMAD in presence of DABCO catalyst and benzanilide in presence of Tf2O and 2-chloropyridine. The prepared molecules were examined for their biological property namely apoptotic and antiproliferative effects through cell cycle arrest using breast cancer cell line of human (MCF-7). Receptor-ligand interactions were studied on human epidermal evolution factor receptor (HER-2) with the help of molecular docking using Autodock 4.2.6 molecular modeling software. All the compounds demonstrated inhibitory effects on cell proliferation in a concentration dependent fashion (20–100 μg/mL). Notably, compound C exhibited highest inhibitory activity and caused inhibition of S and G2 phase in cell cycle arrest via caspase dependent apoptotic pathway in MCF-7 cells lines. Keywords: Pyrimidine, Quinazoline, 1,5-Benzodiazepines, Domino reaction, Anticancer agenthttp://www.sciencedirect.com/science/article/pii/S1018364719318579 |
| spellingShingle | Apoorva Misra Dharma Kishore Ved Prakash Verma Sunil Dubey Subhash Chander Neha Gupta Sameer Bhagyawant Jaya Dwivedi Zeid A. Alothman Saikh Mohammad Wabaidur Swapnil Sharma Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agents Journal of King Saud University: Science |
| title | Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agents |
| title_full | Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agents |
| title_fullStr | Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agents |
| title_full_unstemmed | Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agents |
| title_short | Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agents |
| title_sort | synthesis biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1 5 benzodiazepine as potential anticancer agents |
| url | http://www.sciencedirect.com/science/article/pii/S1018364719318579 |
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