Academic Journal
Discovery of a new potent oxindole multi-kinase inhibitor among a series of designed 3-alkenyl-oxindoles with ancillary carbonic anhydrase inhibitory activity as antiproliferative agents
| العنوان: | Discovery of a new potent oxindole multi-kinase inhibitor among a series of designed 3-alkenyl-oxindoles with ancillary carbonic anhydrase inhibitory activity as antiproliferative agents |
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| المؤلفون: | Ismail, Rania S. M., El Kerdawy, Ahmed M., Soliman, Dalia H., Georgey, Hanan H., Abdel Gawad, Nagwa M., Angeli, Andrea, Supuran, Claudiu T. |
| المساهمون: | Egyptian Russian University |
| المصدر: | BMC Chemistry ; volume 17, issue 1 ; ISSN 2661-801X |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | An optimization strategy was adopted for designing and synthesizing new series of 2-oxindole conjugates. Selected compounds were evaluated for their antiproliferative effect in vitro against NCI-60 cell lines panel, inhibitory effect on carbonic anhydrase (CA) isoforms (hCAI, II, IX and XII), and protein kinases. Compounds 5 and 7 showed promising inhibitory effects on hCA XII, whereas compound 4d was the most potent inhibitor with low nanomolar CA inhibition against all tested isoforms. These results were rationalized by using molecular docking. Despite its lack of CA inhibitory activity, compound 15c was the most active antiproliferative candidate against most of the 60 cell lines with mean growth inhibition 61.83% and with IC 50 values of 4.39, 1.06, and 0.34 nM against MCT-7, DU 145, and HCT-116 cell lines, respectively. To uncover the mechanism of action behind its antiproliferative activity, compound 15c was assessed against a panel of protein kinases (RET, KIT, cMet, VEGFR1,2, FGFR1, PDFGR and BRAF) showing % inhibition of 74%, 31%, 62%, 40%, 73%, 74%, 59%, and 69%, respectively, and IC 50 of 1.287, 0.117 and 1.185 μM against FGFR1, VEGFR, and RET kinases, respectively. These results were also explained through molecular docking. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s13065-023-00994-3 |
| DOI: | 10.1186/s13065-023-00994-3.pdf |
| DOI: | 10.1186/s13065-023-00994-3/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s13065-023-00994-3 https://link.springer.com/content/pdf/10.1186/s13065-023-00994-3.pdf https://link.springer.com/article/10.1186/s13065-023-00994-3/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.A9860BB9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13065-023-00994-3 |
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