Study of the combination of kaurenoic acid and polialtic acid with amphotericin B in promastigote and amastigote forms of Leishmania amazonensis

Abstract

Leishmaniasis is considered a parasitic disease neglected potentially fatal, is caused by different species of the protozoan Leishmania, including species is Leishmania amazonensis. Primary treatment of leishmaniasis is performed using pentavalent antimony (Sb+5) and Sodium Stibogluconate and N-Metilglucamine Antimonate and in cases of resistance of the strain to the primary treatment, other substances such as Pentamidine, Amphotericin B, are used as a second treatment option, despite its high toxicity to the host. In view of the need for new substances with activity against parasites that cause Leishmaniasis, a growing interest in research in order to obtain compounds able to act on the parasites with greater efficacy and lower toxicity. Among all the plants with medicinal properties, the trees of the genus Copaifera are noteworthy because of their pharmacological applications historically proven by popular medicine, including its antiparasitic activity, where it is observed the significant property leishmanicide presented by the oleoresin of several species of this genus. While noting the pharmacological potential of oleoresins of Copaifera, very little is known about the main substances responsible for such activities. However, recent studies with diterpenes kaurenoic acid (16-acid Caure-18-oic acid) (CA) and polialtic acid (15,16-epóxilabda-8 acid (17), 13 (16), 14-triene-19- oic) (PA), found in the fixed part of the oleoresin of most species of Copaifera indicated a significant antiparasitic activity of these substances. Thus, this project is intended to study the effect of the combination of CA and PA each other and between Amphotericin B in promastigotes and amastigotes of L. amazonensis. Initially it will determine the Inhibitory Concentration 50% of parasites (IC50) for each substance. Then the combination study of substances is performed to determine the concentrations that exhibit a synergistic effect. They will also be evaluated the cytotoxic effects and haemolytic of individual substances and combinations. To study the mechanism of action, the morphology of the parasites will be evaluated, and then will be carried out tests to verify death induction evidence of parasites by a similar event to the apoptosis and oxidative stress induction. (AU)