Compostos naftoquinônicos: atividade biológica, fotoprotetora e estudos de interação com ctDNA

Abstract

Currently have been intensifying interest in the chemistry of naphthoquinones because of their wide range of biological activities. The naphthoquinones are part of the class of quinones, which are described as provoking oxidative stress in the cellular environment, which gives them expressive pharmacological activities and the antiproliferative activity being evidence. In this context, the present work aimed at: i) to determine the Sun Protection Factor (SPF); ii) to investigate antioxidant capacity; iii) to determine ADME properties in silico iv) to evaluate the antiproliferative activity, as well as, v) to determine the mechanisms of DNA interaction of naphthoquinone derivatives in vitro using spectroscopic techniques for UV-visible absorption and molecular fluorescence. Initially the SPF-UVB evaluation in vitro was carried out, from which it could be observed that some compounds showed an expressive SPF, in which in the concentration of 200 μM these values ranged from 4.2-25.6. In addition, 3 of the 5 nitrogenated naphthoquinone derivates had an SPF of approximately or higher than the benzophenone-3 standard (24.6). For the study of the antioxidant capacity, it was possible to observe that all compounds analyzed were active as DPPH and ABTS radicals sequesters with a range of between IC50 14.7-26.9 and 14.7-26.9 and 3.8-34.1 μm/mL respectively, being these more active against the second method, evidencing a greater hydrophilic character of the compounds. Then, the ADME in silico properties of the molecules were calculated, demonstrating that these properties are in accordance with rules that predict the efficacy of new drug candidates. The study of antiproliferative activity was performed against nine human tumor cell lines. The compounds were active at a concentration below 200 μg / mL and in some cases there were derivatives with superior or similar activity to the standard drug doxorubicin. The interaction studies showed that the evaluated compounds interact with the ctDNA forming a non-fluorescent supramolecular complex by means of the static quenching mechanism, with a constant (Ksv) of the order of 104 L mol-1 and a binding constant (Kb) of 1.38x103 L mol-1. From the competition studies with hoechst probes and ethidium bromide, it was possible to evaluate the mode of binding of these compounds, which was established to occur via groove.