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

摘要

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)-9 H -purine ( 9 ) had better cytotoxic activity (IC 50 5.4 μM) 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.