Synthesis and anticancer activity of some pyrimidine derivatives with aryl urea moieties as apoptosis-inducing agents

KILIÇ KURT Z., ÖZMEN N., BAKAR ATEŞ F.

BIOORGANIC CHEMISTRY, cilt.101, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 101
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.bioorg.2020.104028
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Pyrimidines, Urea, Anticancer, Apoptosis mechanism, Synthesis, BCR-ABL, KAPPA-B, DESIGN, INHIBITOR, POTENT, DISCOVERY, TARGETS, GROWTH, AURORA
  • Ankara Üniversitesi Adresli: Evet

Özet

A new series of pyrimidine derivatives containing aryl urea moieties was designed and synthesized. The an-ticancer activities of all compounds were evaluated in vitro against colon and prostat cancer cell lines by MTT assay. Among these compounds, 4b exhibited the highest cytotoxic activity against SW480 cancer cell line with IC50 value of 11.08 mu M. Mechanistic studies showed that compound 4b arrested cell cycle at G2/M phase and induced apoptosis through upregulating Bax, Ikb-alpha and cleaved PARP and downregulating Bcl-2 expression levels. Moreover, compound 4b induced loss of mitochondrial membrane potential in SW480 cells. These results suggest that pyrimidine with urea moieties could be a template for designing new anticancer agents.