Exploration of novel 6,8,9-trisubstituted purine analogues: synthesis, in vitro biological evaluation, and their effect on human cancer cells


Creative Commons License

POLAT M. F., İrem D. Ş., Atalay R., TUNÇBİLEK M.

Turkish Journal of Chemistry, cilt.48, sa.1, ss.108-115, 2024 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 48 Sayı: 1
  • Basım Tarihi: 2024
  • Doi Numarası: 10.55730/1300-0527.3643
  • Dergi Adı: Turkish Journal of Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.108-115
  • Anahtar Kelimeler: 6, 8, 9-Trisubstituted purine analogs, cytotoxic activity, human epithelial cancer cells, synthesis
  • Ankara Üniversitesi Adresli: Evet

Özet

Cancer, a leading global cause of mortality, demands continuous advancements in therapeutic strategies. This study focuses on the design and synthesis of a novel series of purine derivatives, specifically 6-(substituted phenyl piperazine)-8-(4-phenoxyphenyl)-9-cyclopentyl purine derivatives (5–11). The motivation behind this endeavor lies in addressing acquired resistance mechanisms in cancer cells, a significant hurdle in current treatment modalities. The synthesis, starting from 4,6-dichloro-5-nitropyrimidine, involves a multi-step process, resulting in seven new purine derivatives. Biological evaluation against human liver, colon, and breast cancer cells (Huh7, HCT116, and MCF7, respectively) was performed using the SRB assay. Among the synthesized analogs, compounds 5 and 6, exhibited notable cytotoxic activity, surpassing clinically used positive controls 5-Fluorouracil and Fludarabine in terms of efficacy. This research underscores the potential of purine derivatives with a phenyl group at the C-8 position as a scaffold for developing compounds with improved anticancer properties. The findings offer insights for future exploration and development of novel agents in cancer pharmaceutical research.