The importance of natural framework in cytotoxicity of diamide derivatives

RETA, G. F.; TERUEL, N. A.; GARCÍA-GONZALEZ, C.; MARTIN, V. S.; GONZALEZ LEON, LETICIA; PADRÓN, J. M.; TONN, C. E.; DONADEL O. J.

San Luis

Congreso; XXX Anual Meeting, Sociedad de Biología de Cuyo; 2012

Several diamides have shown a large number of bioactivities, includingcytotoxic, antibacterial, antifungal, and anti-inflammatoryeffects. In this order we work in synthetize a group of cytotoxiccompounds derivatives from natural products which ensure goodlevels of bioactivity keeping the specificity provided by naturalframework. Diamides were synthetized by Ugi reaction using acetone,aniline or benzylamine and terbutilisocianide. As source ofcarboxyl group was used a natural labdane. To assess the importanceof the natural product reactions were repeated using cinnamicacid. The human solid tumor cell lines were maintained in 25 cm2culture flasks in RPMI 1640 supplemented with inactivated fetalcalf serum and 2 mM L-glutamine in a 37ºC, 5% CO2, 95% humidifiedair incubator. Chemosensititvity tests were performed usingthe SRB assay of the NCI. Each agent was tested in triplicatesat different dilutions in the range 1?100 μM. The results showingvalues lower than 5 μM for labdane derivatives and less than 100μM for the cinnamic acid ones. This study demonstrates the importanceof natural product and suggests that the development of diamidederivatives could be used for therapeutic application