Avaliação da atividade tripanocida da lectina de Vatairea macrocarpa sobre a forma evolutiva Tripomastigota do Trypanosoma cruzi, cepa Y

Abstract

Chagas disease, a protozoosis caused by Trypanosoma cruzi, affects thousands of people worldwide. Classified as a neglected tropical disease, it presents numerous challenges in its management, whether due to the lack of specific medications, accessible diagnostic technologies, or effective transmission control programs. In this scenario, the research aimed to evaluate patented health technologies for treating and diagnosing the disease, as well as to verify the trypanocidal activity of the Vatairea macrocarpa lectin (VML) against the trypomastigote evolutionary forms of T. cruzi, Y strain. To this end, a survey of available patents was conducted in the Cortellis Drug Discovery Intelligence (CDDI) and ESPACENET databases. The trypanocidal action of the VML lectin was tested for cytotoxicity in host cells using LLC-MK2 cell cultures at concentrations of 15.5 μg/mL, 31.2 μg/mL, 62.5 μg/mL, 125 μg/mL, 250 μg/mL, 500 μg/mL, and 1000 μg/mL. Furthermore, the lectin’s action was tested under conditions of carbohydrate-recognition domain (CRD) inhibition by lactose. To evaluate the lectin's affinity for glycoinositolphospholipids (GIPL), in silico tests were performed using molecular docking. Initially, the GIPLs were modeled in the ChemSketch program and optimized using Avogadro software. The protein was retrieved from the Protein Data Bank (PDB). Simulations were performed using the AutoDock Vina server, for which the grid box was established with the following dimensions: center_x = -21.952, y = -19.851, z = -29.065 and size_x = 24, y = 22, size_z = 18. At the end of the study, 31 patents regarding candidate molecules for new drugs were identified, with only two in the clinical trial phase, and 10 patents regarding diagnostic techniques, with universities being the primary applicants. In the in vitro tests, the lectin presented a CC50 2744.00 ± 548.00; when inhibited by lactose, it was not possible to estimate this value for the tested concentrations. The VML lectin presented an LC50 125.70 ± 22.70. The Selectivity Index (SI) of VML was 21.83, making it a candidate for further

studies. Molecular docking indicated a higher affinity for GIPL compared to the saccharide Gal- GalNAc-GlcNAc: GIPL, -2.6 kcal/mol; Gal-GalNAc-GlcNAc, -3.5 kcal/mol; and lactose, -5.1

kcal/mol. The data demonstrate that the saccharides present in the structure bind to the lectin domain of the protein. The identified trypanocidal action is promising, and further investigations to help understand the mechanisms of action involved in the lectin's activity against the parasite are necessary.