Síntese e avaliação de derivados piperidino-benzodioxola planejados como novos candidatos a fármacos leishmanicidas

Abstract

Parasitic diseases remain a serious public health challenge, especially in underdeveloped or developing countries. Among the various existing parasitosis, we can highlight that leishmaniasis is endemic in many countries located in tropical and subtropical regions of the globe. Even today, millions of people become infected and thousands will die as result of complications of the disease if not diagnosed and treated properly. Researches aimed at seeking more effective and safer treatments for diseases considered countries that neglect these are of paramount importance, since the availability of effective and safe medicines is still quite limited and also the pharmaceutical industry sector not demonstrate willingness to investments. Given these facts, the present work aimed at obtaining new candidate prototypes antileishmanial drugs, using as structural model piperine, an amide with natural antileishmanial properties. Thus, we obtained eight piperidine-benzodioxole esters (LFQM 138-145) presenting in their structures the piperidinic and benzodioxolic subunits, common to the compound model, piperine (6). In addition, two carbamates (LFQM 146 and LFQM 147) were also obtained. All compounds had their structures elucidated by spectral techniques IR, NMR and MS. All compounds have been biologically evaluated in vitro against the Leishmania amazonensis promastigotes and values were expressed by IC50 in μM. The most active substances of the ester series were LFQM 144, LFQM 145 and LFQM 139, with IC50 values of 41.06 μM, 42.83 μM and 51.58 μM, respectively. For the carbamate series, the most active was LFQM 146 with IC50 = 43.16 μM, that was equipotent to the evaluated esters LFQM 144 and LFQM 145. All compounds were less active than amphotericin B (IC50 = 5.08 μM) that was used as standard drug in the analysis. The compounds showed low toxicity in the MTT human cell viability assay and LFQM 145 was considered the safer between all the synthetized compounds, with a relation CC50/IC50 = 40,10. Thus, the molecular profile of these compounds is being considered of great interest and may lead future structural optimizations through the discovery of compounds most active and safe