Cancer is the second cause of death in many countries. Several secondary metabolites produced by plants have been discovered and some of them are used on the treatment of cancer. About 70% of the chemotherapies used in the treatment of cancer were inspired by natural products or analogues. In this work, chemical study of the ethyl acetate extracts of leaves and roots of Pluchea sagittalis (Asteraceae) lead to the isolation of Vanillin and Isovanillin. Figure 1A summarizes the structural modifications promoted on Isovanillin structure. All derivatives were evaluated against cancer cell lines: B16F10-Nex2, HL-60, MCF-7, A2058 and HeLa. It was observed that compounds (5), (6), (7), (15), (16), (17) and (18) showed cytotoxic activity. In order to investigate the possible physical-chemical interactions between the drug candidates and the cellular membrane, compound (17), which presented IC50 (µM) ± SD values: 30,4 ± 4,6 for B16F10-Nex2; 26,4 ± 1,3 for HL-60; 19,8 ± 3,0 for A2058; and 18,8 ± 1,1 for HeLa, and higher selectivity index, was deposited in a Langmuir monolayer, self-assembled by the spreading of the DPPC lipid on the air-water interface, and the parameters were analyzed from a physical-chemical approach. The presence of the compounds on the monolayer shifts the isotherm to higher molecular areas, suggesting the penetration of the substance over the lipid monolayer. Furthermore, the data shows that the drug is not expelled until surface pressures higher than 40 mN/m (Figure 1B), which is known as the cell membrane surface pressure. The effect of (17) is evident because provides an increase at the surface pressure to higher areas and raises the threshold that characterizes the transition from liquid-expanded to liquid-condensed phase. We may conclude that (17) destroys the film formed since at higher pressures the curve is shifted to lower areas (Figure 1C). Thus, the behavior observed could be related to the citotoxicity previously detected.