Synthesis of (E)-3,5-dimethyl-4-(R-phenyldiazenyl)isoxazoles was carried out by reaction of β-diketohydrazones, of formula R-C6H4-NHN=C(COCH3)2 with hydroxilammonium chloride, being R= 4-N(CH3)2(1), 4-OH(2), 4-CH3(3), 4-OCH3(4), 4-H(5), 4-Cl(6) 4-Br(7), 4-CO2H(8), 4-CO2CH2CH3(9), 4-COCH3(10), 4-CN(11), 4-NO2(12), 4-CH2CO2CH2CH3(13), 3-Cl(14), 2-OH(15), 2-Cl(16), 2-NO2(17), 2-CO2H(18). All compounds were characterized by EA and spectroscopic methods. The crystalline structure of two compounds was solved by X-rays diffraction method. DFT and TDDFT computations were performed in order to characterize the molecular geometry and the molecular orbitals involved in the transitions. Besides, a biological activity study was performed to evaluate the toxicity of compounds towards human promielocytic leukemia cell line, HL-60, using MTT reduction method. The IC50 values are in a wide concentrations range, 86 - 755 µM. The isoxazoles (3) and (6) were the most cytotoxic. Expression analysis in HL-60 cells were carried out with compounds (3) and (6) by RT-PCR, in order to determine the effect on the expression levels of mRNA codifying for the genes Bcl-2, Bax and p21WAF-1. The isoxazole (3) induced a decrease of the expression of Bcl-2, whereas the isoxazole (6) showed an opposite behaviour. However, these isoxazoles had no effect on mRNA levels of Bax. On the other hand, both isoxazoles increased the levels of p21WAF-1. These results suggest that the cytotoxic activity of the isoxazole (3) would be the sum of effects triggered on promotion of apoptosis and cell cycle arrest, whereas for isoxazole (6) would be mainly through cycle cell arrest.