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  3. Design, synthesis, and cytotoxicity screening of novel pyrazolopyrimidines over renal cell carcinoma (UO-31 cells) as p38α inhibitors, and apoptotic cells inducing activities

Design, synthesis, and cytotoxicity screening of novel pyrazolopyrimidines over renal cell carcinoma (UO-31 cells) as p38α inhibitors, and apoptotic cells inducing activities

  • Eur J Med Chem. 2025 Jan 5:281:117005. doi: 10.1016/j.ejmech.2024.117005.
Sara Y Ewieda 1,  Amr Sonousi 2,  Aliaa M Kamal 3,  Mohamed K Abdelhamid 4
Affiliations

Affiliations

  • 1 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
  • 2 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; University of Hertfordshire hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt.
  • 3 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; Organic Chemistry Department, Faculty of Pharmacy, October University for Modern Science and Arts (MSA), Giza, Egypt.
  • 4 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. Electronic address: mohamed.sayed@pharma.cu.edu.eg.
PMID: 39527892 DOI: 10.1016/j.ejmech.2024.117005
Abstract

A series of novel molecules with pyrazolopyrimidine-4-amine core were designed and synthesized as potential cytotoxic agents over Renal Cell Carcinoma cells (UO-31). Results of cytotoxic activity against UO-31 cells showed that pyrazolopyrimidines 19 and 31 were found to be more cytotoxic than sorafenib (SOR). The cytotoxic activity of these compounds appeared to correlate with their ability to inhibit p38α MAPK which are 2.53- and 2.27- folds more potent than SOR. Moreover, results of the cell cycle analysis as well as the results of annexin-V on the (UO-31) cells showed that pyrazolopyrimidines 19 and 31 had a pro-apoptotic activity higher than SOR by 1.42- and 1.20- folds, respectively. Furthermore, compounds 19 and 31 were found to be effective in arresting the cell cycle throughout the accumulation of the cells at G2/M phase. Finally, the tested compounds decreased the TNF concentration as well as increased the expression of tumor suppressor gene p53, Bax/BCL-2 ratio and caspase 3/7.

Keywords

Anticancer activity; Pyrazolopyrimidines; UO-31 cells; p38α inhibitors.

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