Synthesis of Some Substituted 6-Phenyl Purine Analogues and Their Biological Evaluation as Cytotoxic Agents


Kucukdumlu A., Tuncbilek M., Guven E. B., Atalay R.

ACTA CHIMICA SLOVENICA, cilt.64, sa.3, ss.621-632, 2017 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 64 Sayı: 3
  • Basım Tarihi: 2017
  • Doi Numarası: 10.17344/acsi.2017.3419
  • Dergi Adı: ACTA CHIMICA SLOVENICA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.621-632
  • Anahtar Kelimeler: Antitumor agents, Hepatocellular carcinoma, Heterocycles, Purine derivatives, Structure-activity relationships, CYCLIN-DEPENDENT KINASES, HEPATOCELLULAR-CARCINOMA, ANTIPROLIFERATIVE ACTIVITY, NUCLEOSIDE ANALOGS, CELL-DEATH, DERIVATIVES, INHIBITORS, SORAFENIB, THIOPURINES, MECHANISM
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

A series of 6-(4-substituted phenyl)-9-(tetrahydropyran-2-yl) purines 3-9, 6-(4-substituted phenyl) purines 10-16, 9-((4-substituted phenyl) sulfonyl)-6-(4-substituted phenyl) purines 17-32 were prepared and screened initially for their in vitro anticancer activity against selected human cancer cells (liver Huh7, colon HCT116, breast MCF7). 6-(4-Phenoxyphenyl) purine analogues 9, 16, 30-32, had potent cytotoxic activities. The most active purine derivatives 5-9, 14, 16, 18, 28-32 were further screened for their cytotoxic activity in hepatocellular cancer cells. 6-(4-Phenoxyphenyl)-9(tetrahydropyran-2-yl)-9H-purine (9) had better cytotoxic activity (IC50 5.4 mu M) than the well-known nucleobase analogue 5-FU and known nucleoside drug fludarabine on Huh7 cells. The structure-activity relationship studies reported that the substitution at C-6 positions in purine nucleus with the 4-phenoxyphenyl group is responsible for the anti-cancer activity.