Synthesis and cytotoxicity evaluation of hydroquinazolinone derivates

FAILLACE, M. S.; BRITO, M. R. M.; PEPINO, A. J.; SILVA, T. G.; MILITÃO, G. C. G.; COSTA, J. P.; SILVA, A. P. S. C. L.; ARGÜELLO, G. A.; FREITAS, R. M.; PELÁEZ, W. J.

Córdoba

Congreso; 2014 Reunión Internacional de Ciencias Farmacéuticas RICIFA; 2014

Universidad Nacional de Córdoba-Depto de Farmacia.

We present here the synthesis, purification and structural determination of ten hydroquinazolinone derivatives. Furthermore, the cytotoxic activity was evaluated using three cancerous cell lineages for different carcinomas (HEP-2, larynx carcinoma cells; NCI1-H, lung carcinoma cells and MCF-7, breast carcinoma cells). The cis/trans-2-thioxoquinazolin-4-ones and their 2,4-dione analogs were obtained by conventional synthesis in solution, being the trans isomers more stable than the cis analogs. The measurement of the inhibitory concentration at 50% cell growth (IC50) was the procedure chosen for the determination of the cytotoxicity activity together with a positive control (doxorubicin 2 mg/mL). The results show that all the studied compounds have inhibitory activity irrespective of the tumor cells they act on. The inhibitory activities measured are promising since for all but one specimen, the values are around one order of magnitude below that of the control. The only compound showing values above 25 µg/mL is N-Phenyl-hexahydro-2H-benzo[d][1,3]oxazin-2-imne, whose value (IC50= 84,5 µg/mL) is acting on laying carcinoma cells.