Synthesis of novel substituted purine derivatives and identification of the cell death mechanism

Creative Commons License

Demir Z., Guven E. B., ÖZBEY S., KAZAK C., Atalay R. C., TUNÇBİLEK M.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.89, ss.701-720, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 89
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1016/j.ejmech.2014.10.080
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.701-720
  • Anahtar Kelimeler: Adenine, Purine derivatives, Cytotoxic activity, Senescence, Hepatocellular carcinoma, ADENOSYLHOMOCYSTEINE HYDROLASE INHIBITORS, NUCLEOSIDE ANALOGS, BIOLOGICAL EVALUATION, SENESCENCE, CANCER, 15-LIPOXYGENASE, INDUCTION, SERIES
  • Ankara Üniversitesi Adresli: Evet

Özet

Novel 9-(substituted amino/piperazinoethyl)adenines (4-12), 6-(substituted piperazino/amino)purines (15-27), 9-(p-toluenesulfonyl/cyclopentyl/ethoxycarbonylmethyl)-6-(substituted amino/piperazino)purines (28-34,36,37,38-41) were synthesized and evaluated initially for their cytotoxic activities on liver Huh7, breast T47D and colon HCT116 carcinoma cells. N-6-(4-Trifluoromethylphenyl)piperazine derivative (17) and its 9-(p-toluene-sulfonyI)/9-cyclopentyl analogues (28, 36) had promising cytotoxic activities. Compounds 17, 28 and 36 were further analysed for their cytotoxicity in a panel of a liver cancer cell lines. The compound 36 had better cytotoxic activities (IC50 <= 1 mu M) than the nucleobase 5-FU and nucleosides fludarabine, cladribine, and pentostatine on Huh7 cells. Cytotoxicity induced by 36 was later identified as senescence associated cell death by SA-beta-Gal assay. (C) 2014 Elsevier Masson SAS. All rights reserved.