| Autor: |
El-Sheref EM; Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt., Bräse S; Institute of Biological and Chemical Systems, IBCS-FMS, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany., Tawfeek HN; Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt.; Unit of Occupational of Safety and Health, Administration Office of Minia University, El-Minia 61519, Egypt., Alasmary FA; Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia., Youssif BGM; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of molecular sciences [Int J Mol Sci] 2023 Aug 27; Vol. 24 (17). Date of Electronic Publication: 2023 Aug 27. |
| DOI: |
10.3390/ijms241713300 |
| Abstrakt: |
The reaction of 4-azido-quinolin-2(1 H )-ones 1a - e with the active methylene compounds pentane-2,4-dione ( 2a ), 1,3-diphenylpropane-1,3-dione ( 2b ), and K 2 CO 3 was investigated in this study. This approach afforded 4-(1,2,3-triazol-1-yl)quinolin-2(1 H )-ones 3a - j in high yields and purity. All newly synthesized products' structures were identified. Compounds 3a - j were tested for antiproliferative activity against a panel of four cancer cell lines. In comparison to the reference erlotinib (GI 50 = 33), compounds 3f - j were the most potent derivatives, with GI 50 values ranging from 22 nM to 31 nM. The most effective antiproliferative derivatives, 3f - j , were subsequently investigated as possible multi-target inhibitors of EGFR, BRAF V600E , and EGFR T790M . Compound 3h was the most potent inhibitor of the studied molecular targets, with IC 50 values of 57 nM, 68 nM, and 9.70 nM, respectively. The apoptotic assay results demonstrated that compounds 3g and 3h function as caspase-3, 8, and Bax activators as well as down-regulators of the antiapoptotic Bcl2, and hence can be classified as apoptotic inducers. Finally, compounds 3g and 3h displayed promising antioxidant activity at 10 µM, with DPPH radical scavenging of 70.6% and 73.5%, respectively, compared to Trolox (77.6%). |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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