Dioclea violacea lectin has potent in vitro leishmanicidal activity against Leishmania infantum via carbohydrate recognition domain.

Despite promising advancements in leishmaniasis treatment, existing therapies often face limitations and significant side effects, stimulating the search for novel therapeutic alternatives. In this context, lectins, such as DVL extracted from Dioclea violacea seeds, have emerged as potential candidates due to their diverse biological activities. This study represents the first investigation of the leishmanicidal potential of DVL in vitro against Leishmania infantum. Our results demonstrate that DVL exhibits a leishmanicidal effect (IC50/24 h = 49.37 µg/mL or 2 µM), binding to glycans on L. infantum. Fluorescence assays revealed that DVL can induce the production of reactive oxygen species (ROS) and cause damage to the parasite's membrane. DVL demonstrated a modulating effect when combined with amphotericin B and glucantime, enhancing the activity of these drugs by 40 % and 80 %, respectively. It also showed no cytotoxicity in Raw 264.7 cells and was able to override the toxic effect of amphotericin B on cells and reduce the survival rate of macrophages infected with amastigote forms, as well as their percentage of infection by 31 %. Therefore, DVL shows promise as a treatment for visceral leishmaniasis caused by L. infantum. Our findings provide valuable insights for future therapeutic development targeting leishmania glycans.

Synthetic hydrazones: In silico studies and in vitro evaluation of the antileishmania potential.

Bioprospecting and synthesis of strategically designed molecules have been used in the search for drugs that can be in leishmaniasis. Hydrazones (HDZ) are promising compounds with extensive biological activities. The objective of this work was to perform in silico studies of hydrazones 1-5 and to evaluate their antileishmanial, cytotoxic and macrophage immunomodulatory potential in vitro. Hydrazones were subjected to prediction and molecular docking studies. Antileishmanial protocols on promastigotes and amastigotes of Leishmania amazonensis, cytotoxicity and macrophage immunomodulatory activity were performed. Hydrazones showed a good pharmacokinetic profile and hydrazone 3 and hydrazone 5 were classified as non-carcinogenic. Hydrazone 5 obtained the best conformation with trypanothione reductase. Hydrazone 1 and hydrazone 3 obtained the best mean inhibitory concentration (IC50) values for promastigotes, 4.4-61.96 µM and 8.0-58.75 µM, respectively. It also showed good activity on intramacrophagic amastigotes, with hydrazone 1 being the most active (IC50 = 6.79 µM) with selectivity index of 56. In cytotoxicity to macrophages hydrazone 3 was the most cytotoxic (CC50 = 256.3 ± 0,04 µM), while hydrazone 4 the least (CC50 = 1055.9 ± 0.03 µM). It can be concluded that the hydrazones revealed important pharmacokinetic and toxicological properties, in addition to antileishmania potential in reducing infection and infectivity in parasitized macrophages.

Antileishmania and immunomodulatory potential of cashew nut shell liquid and cardanol.

Conventional treatments for leishmaniasis have caused serious adverse effects, poor tolerance, development of resistant strains. Natural products have been investigated as potential therapeutic alternatives. The cashew nut shell liquid (CNSL) is a natural source of phenolic compounds with several biological activities, where cardanol (CN) is considered one of the most important and promising compounds. This study aimed to evaluate antileishmanial, cytotoxic and immunomodulatory activities of CNSL and CN. Both showed antileishmanial potential, with IC50 for CNSL and CN against Leishmania infantum: 148.12 and 56.74 µg/mL; against Leishmania braziliensis: 85.71 and 64.28 µg/mL; against Leishmania major: 153.56 and 122.31 µg/mL, respectively. The mean cytotoxic concentrations (CC50) of CNSL and CN were 37.51 and 31.44 µg/mL, respectively. CNSL and CN significantly reduced the percentage of infected macrophages, with a selectivity index (SI) >20 for CN. CNSL and cardanol caused an increase in phagocytic capacity and lysosomal volume. Survival rates of Zophobas morio larvae at doses of 3; 30 and 300 mg/kg were: 85%, 75% and 60% in contact with CNSL and 85%, 60% and 40% in contact with CN, respectively. There was a significant difference between the survival curves of larvae when treated with CN, demonstrating a significant acute toxicity for this substance. Additional investigations are needed to evaluate these substances in the in vivo experimental infection model.