Synthesis and antitumor activity of pyrido [2,3-d]pyrimidine and pyrido[2,3-d] [1,2,4]triazolo[4,3-a]pyrimidine derivatives that induce apoptosis through G1 cell-cycle arrest
| Autor: | Radwa A. Eladwy, Hatem A. Abdel-Aziz, Mohamed Fares, Sahar M. Abou-Seri, Mohieldin M. Youssef, Safinaz E. Abbas |
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| Rok vydání: | 2014 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cell cycle checkpoint Pyrimidine Stereochemistry Antineoplastic Agents Apoptosis Chemistry Techniques Synthetic Prostate cancer chemistry.chemical_compound Cell Line Tumor Drug Discovery medicine Humans Cytotoxic T cell Cyclin D1 Pharmacology Caspase 3 Chemistry Organic Chemistry Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase 6 General Medicine Triazoles Cell cycle medicine.disease G1 Phase Cell Cycle Checkpoints Molecular biology Gene Expression Regulation Neoplastic Pyrimidines Cell culture G1 phase Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | European Journal of Medicinal Chemistry. 83:155-166 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2014.06.027 |
| Popis: | New series of 2-(2-arylidenehydrazinyl)pyrido[2,3-d]pyrimidines 5a–e and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines 6–15 were synthesized and evaluated for their cytotoxic activity against two cancer cell lines, namely PC-3 prostate cancer and A-549 lung cancer. Some of the tested compounds displayed high growth inhibitory activity against PC-3 cells. Whereas, compounds 5b and 15f showed relatively potent antitumor activity against PC-3 and A-549 cell lines. In particular, 4-(3-acetyl-5-oxo-6-phenyl-8-(thiophen-2-yl)pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-1(5H)-yl)benzenesulfonamide 15f exhibited superior antitumor activity against both cell lines at submicromolar level (IC50 = 0.36, 0.41 μM, respectively). Moreover, the potential mechanisms of the cytotoxic activity of the promising compound 15f on the more sensitive cell line PC-3 were studied. The data indicated that 15f was able to cause cell cycle arrest at least partly through enhancing the expression level of the cell cycle inhibitor p21 and induced cancer cell apoptosis via caspase-3 dependent pathway. |
| Databáze: | OpenAIRE |
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