Synthesis of Novel Pyrazole-Oxindole Conjugates with Cytotoxicity in Human Cancer Cells via Apoptosis

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...

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Bibliographic Details
Published in:Chemistry & biodiversity 2023-09, Vol.20 (9), p.e202300843-e202300843
Main Authors: Jain, Pravesh M, Gutierrez, Denisse A, Kumar, Sujeet, Aguilera, Renato J, Karki, Subhas S
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Annexin V
Antineoplastic Agents - chemistry
Apoptosis
Cell activation
Cell cycle
Cell death
Cell Line, Tumor
Conjugates
Cytotoxic agents
Cytotoxicity
DNA fragmentation
Flow cytometry
G1 phase
Humans
Leukemia
Lymphatic leukemia
Lymphocytes
Lymphocytes T
Neoplasms
NMR
Nuclear magnetic resonance
Oxindoles - pharmacology
Pyrazole
Pyrazoles
Pyrazoles - pharmacology
Reactive oxygen species
Reactive Oxygen Species - metabolism
Spectroscopy, Fourier Transform Infrared
Toxicity
Tumor cell lines
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Summary: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 CC 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.
ISSN:1612-1872
1612-1880
1612-1880
DOI:10.1002/cbdv.202300843