Design, Synthesis and In Vitro Cytotoxic Activity of New 6,9-Disubstituted Purine Analogues.

A series of new 6,9-disubstituted purine analogs with 4-substituted piperazine at C-6 and 4-substituted benzyl at N-9 were designed and synthesized in four steps. All synthesized compounds (7-26) were screened initially for their in vitro anticancer activity on Huh7 liver, HCT116 colon and MCF7 breast carcinoma cell lines. Cytotoxic bioactivity studies revealed that all compounds screened, with compound 19 being the exception, were found to have promising cytotoxic activities at IC50 range of 0.05-21.8 ∆M against cancer cells Huh7, HCT116 and MCF7. Among the prepared purine analogs, two of them (12 and 22) exhibited excellent cytotoxic activities, with IC50 0.08-0.13 ∆M, on Huh7 cells comparable to camptothecin (CPT) and better than cladribine, fludarabine and 5-FU. Afterwards, the evaluation of cytotoxicity of the most potent purine analogs was screened against further hepatocellular cancer (HCC) cell lines. The 6-(4-(4-trifluoromethylphenyl)piperazine (12) and 6-(4-(3,4-dichlorophenyl)piperazine analogs (25) displayed a significant IC50 values (IC50 < 0.1-0.13 ∆M) comparable to CPT and better cytotoxic bioactivity when compared with 5-FU, cladribine and fludarabine on HCC cells (Huh7 and HepG2).

Synthesis of novel 6-substituted amino-9-(ß-d-ribofuranosyl)purine analogs and their bioactivities on human epithelial cancer cells.

New nucleoside derivatives with nitrogen substitution at the C-6 position were prepared and screened initially for their in vitro anticancer bioactivity against human epithelial cancer cells (liver Huh7, colon HCT116, breast MCF7) by the NCI-sulforhodamine B assay. N6-(4-trifluoromethylphenyl)piperazine analog (27) exhibited promising cytotoxic activity. The compound 27 was more cytotoxic (IC50 = 1-4 µM) than 5-FU, fludarabine on Huh7, HCT116 and MCF7 cell lines. The most potent nucleosides (11, 13, 16, 18, 19, 21, 27, 28) were further screened for their cytotoxicity in hepatocellular cancer cell lines. The compound 27 demonstrated the highest cytotoxic activity against Huh7, Mahlavu and FOCUS cells (IC50 = 1, 3 and 1 µM respectively). Physicochemical properties, drug-likeness, and drug score profiles of the molecules showed that they are estimated to be orally bioavailable. The results pointed that the novel derivatives would be potential drug candidates.

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

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 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.

DNA binding, antioxidant and antimicrobial activities of homo- and heteronuclear copper(II) and nickel(II) complexes with new oxime-type ligands.

Some homo- and heteronuclear Cu(II) and Ni(II) complexes of new oxime-type ligands were tested against several pathogenic microorganisms to assess their antimicrobial potentials. The antimicrobial activities of complexes were evaluated in terms of minimum inhibitory concentration (MIC; µg/µL) and it was observed that the complexes possess moderate antimicrobial properties. The binding of the complexes with DNA were also investigated by using UV-Vis spectroscopy. It was seen that three of the complexes could bind to DNA through an intercalative mode while the other complexes could have other mechanisms. Furthermore, the antioxidant efficiencies of the metal complexes were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavening activities. Due to the observed IC(50) values, they are potential drugs to eliminate the radicals.