XLIII Annual Meeting of SBBq th th Foz do Iguaçu, PR, Brazil, May 17 to 20 , 2014 Evaluation of a pyranonaphthoquinone against six cancer cell lines and Ehrlich tumor carcinoma Oliveira, M.E. 1; Bücker, N.C.F. 2; Rodrigues, P.C. 1; Will, L.S.E.P. 2; Ferreira, S.B 3.; Pedrosa, C.R. 2; Silva-Jr, F.P. 1 1 Laboratório de Bioquímica de Proteínas e Peptídeos, IOC, FIOCRUZ, Rio de Janeiro, Brazil; 2 Laboratório de Bioquímica Experimental, UFSC, Florianópolis, Brazil; 3 Instituto de Química, UFRJ, Rio de Janeiro, Brazil. INTRODUCTION. Cancer is the second cause of death in the world and the development of new chemotherapeutics is urgently required. Natural and synthetic derivatives of quinone have been widely investigated for cancer therapy, especially naphthoquinones. In this view, SQ17, was identified as a cytotoxic compound among a series of pyranonaphthoquinones derived from β-lapachone obtained in our group by chemical synthesis. SQ17 was highly active (IC50 2-5 µM) against four cancer cell lines (HL-60, SF-295, MDA-MB-435 and HCT-8) and also showed moderate human DNA topoisomerase I inhibition. In this study, we further investigated the cytotoxic effects of SQ17 in additional six cancer cell lines (MOLT4, CEM, K562, KG1, HT29 and MCF-7) and evaluated whether it has antitumor effects against the Ehrlich ascites carcinoma in a mouse model. MATERIALS AND METHODS. For the in vitro assay, SQ17 was added in varying concentrations to the cell culture disposed in 96well plates and cell death was evaluated after 48h incubation by the Alamar Blue protocol. For the in vivo assay, mice were inoculated with Ehrlich carcinoma cells; i.p. treatments (saline; 1 mg/Kg; 2 mg/Kg; 5 mg/Kg) were done every 24h for 9 days. Tumor growth inhibition was investigated macroscopically from the change in the abdominal circumference measured on days 0 and 10. Half of all mice were euthanized and angiogenesis inhibition was evaluated. The remaining animals were kept alive to evaluate survival parameters. RESULTS AND DISCUSSION. SQ17 was toxic (IC50 < 20 µM) for all cell lines. In vivo, we found a slight reduction of tumor growth and angiogenesis in groups treated with SQ17 and mice treated with 5 mg/Kg had a 39% increase in survival. CONCLUSION. Regardless of the cell line used, SQ17 showed cytotoxic potential. Besides, the in vivo results indicated this compound has a promising pharmacological profile thus motivating further studies. Key-words: cancer; beta-lapachone, pyranonaphtoquinone Acknowledgments: CNPq; FIOCRUZ; FAPERJ.