Synthesis of novel substituted purine derivatives and identification of the cell death mechanism
- Eur J Med Chem. 2015 Jan 7:89:701-20. doi: 10.1016/j.ejmech.2014.10.080.
- 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey.
- 2. Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey.
- 3. Department of Engineering Physics, Faculty of Engineering, Hacettepe University, 06800 Beytepe, Ankara, Turkey.
- 4. Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayıs University, 55139 Kurupelit, Samsun, Turkey.
- 5. Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey. Electronic address: [email protected].
- 6. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey. Electronic address: [email protected].
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-sulfonyl)/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 μM) 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-β-Gal assay.