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, vol.64, no.3, pp.621-632, 2017 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 64 Issue: 3
  • Publication Date: 2017
  • Doi Number: 10.17344/acsi.2017.3419
  • Journal Name: ACTA CHIMICA SLOVENICA
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.621-632
  • Keywords: 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
  • Middle East Technical University Affiliated: Yes

Abstract

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.