INTRODUCTION AND OBJECTIVES: Oral cancer is the fourth most prevalent in Brazil southeast. Traditional chemotherapy presents many side effects. Natural or synthetic naphthoquinones have cytotoxic potential. Substances containing acridine show great antineoplastic action. Combining naphthoquinones and acridines may achieve new good therapeutic agents. Objectives: to determine cytotoxicity and selectivity in OSSC and Fibroblast lines, and substance’s stability. Perform in silico analysis. Determine acute toxicity in mice. MATERIAL AND METHODS: 15 substances (NAC 1-15) synthesized at Instituto de Quimica da Universidade Federal Fluminense hybridizing acridine with 2-amino-1,4-naphthoquinone. Cell viability and Selectivity Index was calculated based on MTT assay results in OSCC9, 4, 25 and Human Fibroblast. For stability assay, the substance was tested after exposure at 37°C. Carboplatin, Shikonin, Lapachol were positive and DMSO negative controls. In silico analysis was performed using ORISIS, ADMETsar and Mollinspiration servers. Furthermore, collaboratively, the most active substance was submitted to molecular modeling using reverse docking approach. In vivo acute toxicity approved by CEUA / UFF, protocol #982. RESULTS AND CONCLUSION: NAC3 exhibit the best results. The IC50 in SCC9 was 14,71µM. In fibroblast treated with NAC3 with 2xIC50 the viability was 72,70% and the IC50 is 87,99µM. In OSCC4 the IC50 was 53,75µM and in OSCC25 21,52µM. Thus, the seIectivity index calculated is 2.933. NAC3 stability: Instable in the first hour and stable in the following hours exposed to heat. In silico results: cLOGP: 5,72; solubility: -7,2; Pg-P substrate: -0,723; CYP3A4 inhibitor: +0,670. Acute toxicity using NAC3: no deaths documented. It’s concluded that NAC3 is selective and thermolabile. In silico analysis points to good feature as drug. Also, the reverse docking reveals that NAC3 binds to Topoisomerase IIα, RSK2 and PKM2 in a similar manner to known inhibitors of these targets. In vivo results demonstrate it was no acutely toxic. There are ongoing experiments to clarify the possible death pathway involved.