INTRODUCTION AND OBJECTIVES: Oral cancer is the fifth most prevalent in men in Brazil until 2018. Traditional chemotherapy presents many side effects. Natural or synthetic naphthoquinones have proven cytotoxic potential. Substances containing acridines show great antineoplastic action. Synthesizing substances combining naphthoquinones and acridines is an attractive planning strategy for new therapeutics agents. The objectives are: determine cytotoxicity and selectivity of 15 substances in OSSC and Fibroblast lines. Submit that most active to molecular biology assays. Characterize its stability. Perform in silico evaluation of chemical and biologic properties. MATERIAL AND METHODS: 15 substances (NAC 1-15) synthesized collaboratively with Instituto de Quimica da Universidade Federal Fluminense, hybridizing acridine with 2-amino-1,4-naphthoquinone. Tested in MTT assay in OSCC9 and human fibroblasts-treated at 2xIC50 of those with best results, select the 3 most selective and determine IC50 in fibroblasts, OSCC4 and 25, finally calculate the Selectivity Index (S.I). In order to stipulate stability, OSCC9 cell line were treated with that most active substance at 2XIC50 concentration, exposed to 37°C at different periods of time. Carboplatin and DMSO were positive and negative controls for all experiments. In silico results were obtained at ORISIS, ADMETsar and Mollinspiration servers. RESULTS AND CONCLUSION: IC50 values in µM for SCC9 cells: NAC1 (14,69±0,011); NAC2 (51,57±0,189); NAC3 (14,71±0,126); NAC4 (5,86±0,1575); NAC5 (4.105±0,070); NAC6 (4.467±0,070); NAC7 (2.066±0,072); NAC8 (8.934±0,096); NAC9 (2.218±0,123); NAC10 (4.754±0,068); NAC11 (7.636±0,096); NAC12 (6.844±0,1415); NAC13 (7.206±0,086); NAC14 (5.906±0,145); NAC15 (3.323±0,132). Fibroblasts viability: NAC5 (82%), NAC7 (73,68%), NAC3 (72,70%) e NAC9 (67,77%), NAC4 (50,99%), NAC6 (53,72%), NAC8 (55,62%) e NAC10 (57,45%). IC50 in OSCC4: NAC3 (53,75±0,096), NAC5 (18,86±0,093), NAC7 (10,99±0,658); and OSCC25: NAC3 (21,52±0,071), NAC5 (11,50±0,059) e NAC7 (7,41±0,069). SeIectivity Index: NAC3 (2.933), NAC5 (2.050) e NAC7 (1.152). NAC3 stability: in the first hour of exposure, the substance showed instability then proved stable in the other hours, unlike controls, wich remained constant during 48 hours at 37°C. In silico results: cLOGP: 5,72; solubility: -7,2; Pg-P substrate: -0,723; CYP3A4 inhibitor: +0,670. Observing the data presented above, it is concluded that NAC3 stands out with the highest selectivity index. In addition it’s thermolabile, losing some effectiveness in 1 hour at 37°C. Finally, in silico analysis demonstrate good feature as drug (able to pass through plasmatic membrane, well absorved, CYP34A and Pg-P inhibitor). Molecular assays are in progress to clarify the induced death pathway.