Dados do Trabalho

Título

ANTI-LEISHMANIAL AND CYTOTOXIC ACTIVITY OF NEW MORITA-BAYLIS-HILLMAN ADDUCTS

Introdução

Leishmaniases are a complex of diseases caused by protozoan parasites of the genus Leishmania, and can be divided into two major groups, cutaneous leishmaniasis and visceral leishmaniasis. The current treatment of visceral leishmaniasis (VL) has limitations due to drug toxicity and/or high cost, along with the emergence of parasite resistance. Given the toxicity of available medications.

Objetivo (s)

The objective of this study was to evaluate the anti-Leishmania activity of Morita-Baylis-Hillman adducts against L. infantum species and their potential cytotoxic effects on human erythrocytes.

Material e Métodos

In the present study, all compounds were tested at concentrations ranging from 3.12 µM to 400 µM in triplicates, across three independent experiments to obtain the cell viability rate in promastigote and axenic amastigote forms of the parasite, using the colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) method. Additionally, the hemolytic rates of the compounds were evaluated on human erythrocytes, using the Mean Inhibitory Concentration (IC50). The reference drug Amphotericin B was used as a positive control. All statistical analyses were performed using GraphPad Prism software (San Diego, USA). This study was approved by the Ethics Committee for Research on Human Subjects of Lauro Wanderley University Hospital/UFPB (CAAE: 17813013.8.0000.5183).

Resultados e Conclusão

A series of 9 molecules resulting from the Morita-Baylis-Hillman reaction were tested, namely: AIM02, AIM03, AIM12, AIM21, AIM22, AIM23, AIM41, AIM51, and AIM52, with potential anti-Leishmania effects. However, only AIM52 showed success in inhibiting growth and inducing death in promastigote forms, achieving an IC50 of 37.68 µM. The same compound also exhibited significant mortality on amastigote forms of the parasite, with an average EC50 of 4.02 µM compared to the negative control group. Additionally, we also observed low hemolytic activity of this compound, with average erythrocyte lysis percentages below 2%. This potential activity could be considered an important advancement in the study of this class of compounds, serving as a promising candidate for the development of new, more effective, safe, and selective leishmanicidal drugs for humans.

Palavras Chave

Synthetic compounds; Leishmaniases; Pharmacological target