| Institution: | 1. Department of Pharmaceutical Chemistry, KLE College of Pharmacy (A Constituent Unit of KLE Academy of Higher Education & Research-Belagavi), Rajajinagar, Bengaluru, Karnataka, India-, 560010
Equal first author.;2. Cellular Characterization and Biorepository Core Facility, Border Biomedical Research Center, Department of Biological Sciences, College of Science, The University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968-0519 USA;3. Department of Pharmaceutical Chemistry, KLE College of Pharmacy (A Constituent Unit of KLE Academy of Higher Education & Research-Belagavi), Rajajinagar, Bengaluru, Karnataka, India-, 560010 |
| Abstract: | A novel series of pyrazole-oxindole conjugates were prepared and characterized as potential cytotoxic agents by FT-IR, NMR and HR-MS. The cytotoxic activity of these compounds was tested in the Jurkat acute T cell leukemia, CEM acute lymphoblastic leukemia, MCF10 A mammary epithelial and MDA-MB 231 triple negative breast cancer cell lines. Among the tested conjugates, 5-methyl-3-((3-(1-phenyl)-3-(p-tolyl)-1H-pyrazol-4-yl)methylene)indolin-2-one 6h emerged as the most cytotoxic with a CC50 of 4.36+/−0.2 μM against Jurkat cells. The mechanism of cell death induced by 6h was investigated through the Annexin V-FITC assay via flow cytometry. Reactive oxygen species (ROS) accumulation, mitochondrial health and the cell cycle progression were also evaluated in cells exposed to 6h . Results demonstrated that 6h induces apoptosis in a dose-response manner, without generating ROS and/or altering mitochondrial health. In addition, 6h disrupted the cell cycle distribution causing an increase in DNA fragmentation (Sub G0-G1), and an arrest in the G0-G1 phase. Taken together, the 6h compound revealed a strong potential as an antineoplastic agent evidenced by its cytotoxicity in leukemia cells, the activation of apoptosis and restriction of the cell cycle progression. |
