2. Academic Validation
  3. Discovery of novel thiazolopyrimidine derivatives targeting topoisomerase II: Design, synthesis, antiproliferative evaluation, molecular docking and apoptosis inducing activity

Discovery of novel thiazolopyrimidine derivatives targeting topoisomerase II: Design, synthesis, antiproliferative evaluation, molecular docking and apoptosis inducing activity

  • Bioorg Chem. 2025 Jun 6:163:108672. doi: 10.1016/j.bioorg.2025.108672.
Sara Y Ewieda 1,  Mo'men Salem 2,  Ahmed Elshewy 3,  Mohnad Abdalla 4,  May El-Manawaty 5,  Hoda Khalifa Abdelhady 6,  Haredy Hassan Haredy 6,  Wael A A Fadaly 7,  Mamdouh F A Mohamed 8,  Mohamed T M Nemr 9
Affiliations

Affiliations

  • 1 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini street, 11562 Cairo, Egypt. Electronic address: sara.eweda@pharma.cu.edu.eg.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sinai University - Arish branch, Arish 45511, Egypt.
  • 3 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini street, 11562 Cairo, Egypt; Department of Natural and Applied Sciences, College of Arts and Sciences, The American University of Iraq-Baghdad (AUIB), Baghdad, Iraq.
  • 4 Pediatric Research Institute, Children's Hospital Affiliated to Shandong University, Jinan, Shandong 250022, PR China.
  • 5 Pharmacognosy Department, National Research Centre, Egypt.
  • 6 Pharmacology Department, Faculty of Medicine, Al-Azhar University, Assuit, Egypt.
  • 7 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
  • 8 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, 82524 Sohag, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Valley University, New Valley 72511, Egypt.
  • 9 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini street, 11562 Cairo, Egypt.
PMID: 40482357 DOI: 10.1016/j.bioorg.2025.108672
Abstract

Two new sets of thiazolopyrimidines IIa-h, IVa-d were designed, synthesized, and screened for their Anticancer activity against MCF-7 breast Cancer adenocarcinoma, HCT116 colorectal Cancer, and HepG2 hepatic Cancer. The safety of the newly synthesized compounds was tested using normal cells (BJ). Compounds IIa, IId, and IVa showed exceptional cytotoxic activity against both MCF-7 and HepG2, with IC50 ranges of (24.52-30.22 & 21.49-34.09 μM), respectively, compared to Doxorubicin IC50 (32.36 & 50.29 μM), respectively. Furthermore, they exhibited significant selectivity towards the tested Cancer cells (SI values 1.7-4.4) compared to doxorubicin (SI values 0.8-1.8). Additionally, thiazolopyrimidines IIa, IId, and IVa showed potent Topoisomerase II inhibitory activity (IC50 1.23, 0.94, and 1.72 μM, respectively) in comparison with reference compound doxorubicin (IC50 3.08 μM). Cell cycle analysis showed that the most potent derivative IId induces cell cycle arrest at the G1 phase, leading to inhibition of cell proliferation and Apoptosis. Docking study of thiazolopyrimidines IIa, IId, and IVa showed that they could fit well in the pocket in a similar pattern to etoposide, which accounts for their high potency.

Keywords

Antiproliferative; Apoptosis; Molecular docking; Thiazolopyrimidines; Topoisomerase II.

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