ABSTRACT Background: Several studies have pointed out that certain snake venoms contain compounds presenting cytotoxic activities that selectively interfere with cancer cell metabolism. In this study, Pseudocerastes persicus venom and its fractions were investigated for their anticancer potential on lung cancer cells. Methods: Lung cancer cells (A549) and normal fibroblast cells (Hu02) were treated with the P. persicus venom and its HPLC fractions and the cell cytotoxic effects were analyzed using MTT and lactate dehydrogenase release assays. Apoptosis was determined in venom-treated cell cultures using caspase-3 and caspase-9 assay kits. Results: The treatment of cells with HPLC fraction 21 (25-35 kDa) of P. persicus venom resulted in high LDH release in normal fibroblast cells and high caspase-3 and caspase-9 activities in lung cancer cells. These results indicate that fraction 21 induces apoptosis in cancer cells, whereas necrosis is predominantly caused by cell death in the normal cells. Fraction 21 at the final concentration of 10 μg/mL killed approximately 60% of lung cancer cells, while in normal fibroblast cells very low cell cytotoxic effect was observed. Conclusion: HPLC fraction 21 at low concentrations displayed promising anticancer properties with apoptosis induction in the lung cancer cells. This fraction may, therefore, be considered a promising candidate for further studies.

A condensação direta de benzeno-1,2-diaminas (4-R-Ph-(NH2)2, onde R = H, Me, Cl e NO2) e 1,2-dicarbonil (R'-CO-CO-R', onde R' = Ph, 4-MeO-Ph e Me) foi realizada com excelentes rendimentos (95-100%) usando (NH4Cl-CH3OH) como sistema catalítico brando, eficiente, de boa relação custo-benefício, fácil obtenção, isento de ácido e de metal e ambientalmente amigável, a temperatura ambiente. O procedimento pode ser realizado para diversas quinoxalinas e a natureza do grupo funcional no anel aromático das 1,2-diaminas exerce uma forte influência no tempo e rendimento da reação. A eficiência da condensação pode ser regulada também pela quantidade de catalisador e tempo de reação.

The direct condensation of various benzene-1,2-diamines [4-R-Ph-(NH2)2, where R = H, Me, Cl and NO2] and 1,2-dicarbonyl compounds (R'-CO-CO-R', where R' = Ph, 4-MeO-Ph and Me) has been successfully achieved mostly in excellent yields (95-100%) using (NH4Cl-CH3OH) as a mild, efficient, cost-effective, readily available, acid-free, metal-free and eco-friendly catalyst system at room temperature. The procedure can be performed for a broad scope of quinoxalines, however, the nature of the functional group on the aromatic ring of 1,2-diamine exerts a strong influence on the time and the reaction yield. The condensation efficiency could be further regulated by the amount of catalyst and reaction time.