Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studies
Two new series of symmetric (1a-h) and asymmetric (2a-l) 1,4-DHP derivatives were designed, synthesised, and evaluated as anticancer agents. In vitro anticancer screening of target compounds via National cancer institute “NCI” revealed that analogues 1g, 2e, and 2l demonstrated antiproliferative act...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2120478 |
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| author | Mohamed H. Saad Tarek F. El-Moselhy Nabaweya S, El-Din Ahmed B. M. Mehany Amany Belal Mohammed A. S. Abourehab Haytham O. Tawfik Mervat H. El-Hamamsy |
| author_facet | Mohamed H. Saad Tarek F. El-Moselhy Nabaweya S, El-Din Ahmed B. M. Mehany Amany Belal Mohammed A. S. Abourehab Haytham O. Tawfik Mervat H. El-Hamamsy |
| author_sort | Mohamed H. Saad |
| collection | DOAJ |
| description | Two new series of symmetric (1a-h) and asymmetric (2a-l) 1,4-DHP derivatives were designed, synthesised, and evaluated as anticancer agents. In vitro anticancer screening of target compounds via National cancer institute “NCI” revealed that analogues 1g, 2e, and 2l demonstrated antiproliferative action with mean growth inhibition percentage “GI%” = 41, 28, and 64, respectively. The reversal doxorubicin (DOX) effects of compounds 1g, 2e, and 2l were examined and illustrated better cytotoxic activity with IC50 =1.12, 3.64, and 3.57 µM, respectively. The most active anticancer analogues, 1g, 2e, and 2l, were inspected for their putative mechanism of action by estimating their epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2), and Bruton’s tyrosine kinase (BTK) inhibitory activities. Furthermore, the antimicrobial activity of target compounds was assessed against six different pathogens, followed by determining the minimum inhibitory concentration “MIC” values for the most active analogues. Molecular docking study was achieved to understand mode of interactions between selected inhibitors and different biological targets. |
| first_indexed | 2024-04-11T12:00:21Z |
| format | Article |
| id | doaj.art-08c13f6eb467482ba301125ea5211ccd |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-11T12:00:21Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-08c13f6eb467482ba301125ea5211ccd2022-12-22T04:24:53ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712489251110.1080/14756366.2022.2120478Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studiesMohamed H. Saad0Tarek F. El-Moselhy1Nabaweya S, El-Din2Ahmed B. M. Mehany3Amany Belal4Mohammed A. S. Abourehab5Haytham O. Tawfik6Mervat H. El-Hamamsy7The Egyptian Ministry of Health, Tanta, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, EgyptZoology Department, Faculty of Science, Al-Azhar University, Cairo, EgyptMedicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, EgyptTwo new series of symmetric (1a-h) and asymmetric (2a-l) 1,4-DHP derivatives were designed, synthesised, and evaluated as anticancer agents. In vitro anticancer screening of target compounds via National cancer institute “NCI” revealed that analogues 1g, 2e, and 2l demonstrated antiproliferative action with mean growth inhibition percentage “GI%” = 41, 28, and 64, respectively. The reversal doxorubicin (DOX) effects of compounds 1g, 2e, and 2l were examined and illustrated better cytotoxic activity with IC50 =1.12, 3.64, and 3.57 µM, respectively. The most active anticancer analogues, 1g, 2e, and 2l, were inspected for their putative mechanism of action by estimating their epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2), and Bruton’s tyrosine kinase (BTK) inhibitory activities. Furthermore, the antimicrobial activity of target compounds was assessed against six different pathogens, followed by determining the minimum inhibitory concentration “MIC” values for the most active analogues. Molecular docking study was achieved to understand mode of interactions between selected inhibitors and different biological targets.https://www.tandfonline.com/doi/10.1080/14756366.2022.21204781,4-DHPsanticancermultidrug resistance (MDR)P-glycoproteinreceptor tyrosine kinases (RTKs)apoptosis |
| spellingShingle | Mohamed H. Saad Tarek F. El-Moselhy Nabaweya S, El-Din Ahmed B. M. Mehany Amany Belal Mohammed A. S. Abourehab Haytham O. Tawfik Mervat H. El-Hamamsy Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studies Journal of Enzyme Inhibition and Medicinal Chemistry 1,4-DHPs anticancer multidrug resistance (MDR) P-glycoprotein receptor tyrosine kinases (RTKs) apoptosis |
| title | Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studies |
| title_full | Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studies |
| title_fullStr | Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studies |
| title_full_unstemmed | Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studies |
| title_short | Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studies |
| title_sort | discovery of new symmetrical and asymmetrical nitrile containing 1 4 dihydropyridine derivatives as dual kinases and p glycoprotein inhibitors synthesis in vitro assays and in silico studies |
| topic | 1,4-DHPs anticancer multidrug resistance (MDR) P-glycoprotein receptor tyrosine kinases (RTKs) apoptosis |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2120478 |
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