Toward New Therapeutics for Visceral Leishmaniasis: Efficacy and Mechanism of Action of Amides Inspired by Gibbilimbol B.

The problems with current strategies to control canine visceral Leishmaniasis (CVL), which include the euthanasia of infected animals, and also the toxicity of the drugs currently used in human treatments for CVL, add urgency to the search for new therapeutic agents. This study aimed to evaluate the activity against of 12 amides that are chemically inspired by gibbilimbol B, a bioactive natural product that was initially obtained from . Three of these compounds--(2-ethylhexyl)-4-chlorobenzamide (), -(2-ethylhexyl)-4-nitrobenzamide (), and -(2-ethylhexyl)-4-(-butyl)benzamide () -demonstrated activity against the intracellular amastigotes without toxicity to mammalian host cells (CC > 200 μM); compounds , , and resulted in EC values of 12.

Saturated Iso-Type Fatty Acids from the Marine Bacterium with Anti-Trypanosomal Potential.

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new anti-trypanosomal compounds, we investigated the potential of the metabolites from the bacteria living in the corals and sediments of the southeastern Brazilian coast. Three corals, , , and sediments yielded 11 bacterial strains that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera-, , , , and To conduct this study, EtOAc extracts were prepared and tested against The crude extracts showed IC values ranging from 15 to 51 μg/mL against the trypomastigotes.

Andrographolide: A Diterpenoid from Identified as a New Hit Compound against Using Machine Learning and Experimental Approaches.

American Trypanosomiasis, also known as Chagas disease, is caused by the protozoan and exhibits limited options for treatment. Natural products offer various structurally complex metabolites with biological activities, including those with anti- potential. The discovery and development of prototypes based on natural products frequently display multiple phases that could be facilitated by machine learning techniques to provide a fast and efficient method for selecting new hit candidates.

ATP6V0d2 controls Leishmania parasitophorous vacuole biogenesis via cholesterol homeostasis.

V-ATPases are part of the membrane components of pathogen-containing vacuoles, although their function in intracellular infection remains elusive. In addition to organelle acidification, V-ATPases are alternatively implicated in membrane fusion and anti-inflammatory functions controlled by ATP6V0d2, the d subunit variant of the V-ATPase complex. Therefore, we evaluated the role of ATP6V0d2 in the biogenesis of pathogen-containing vacuoles using ATP6V0d2 knock-down macrophages infected with the protozoan parasite Leishmania amazonensis.

Interaction of Trastuzumab with biomembrane models at air-water interfaces mimicking cancer cell surfaces.

Trastuzumab (Tmab) is a monoclonal antibody administered as targeted therapy for HER2-positive breast cancer whose molecular interactions at the HER2 receptor microenvironment are not completely clarified yet. This paper describes the influence of Tmab in the molecular organization of films of biological-relevant molecules at the air water interface. For that, we spread components of tumorigenic and non-tumorigenic cells directly on the air-water interface.

Characterization and role of the 3-methylglutaconyl coenzyme A hidratase in Trypanosoma brucei.

Trypanosoma brucei, the agent of African Trypanosomiasis, is a flagellated protozoan parasite that develops in tsetse flies and in the blood of various mammals. The parasite acquires nutrients such as sugars, lipids and amino acids from their hosts. Amino acids are used to generate energy and for protein and lipid synthesis.