Integração de abordagens in silico e in vivo na prospecção de moluscicidas de nova geração

Abstract

Human schistosomiasis is a neglected tropical disease transmitted through Biomphalaria glabrata, the intermediate host mollusk of Schistosoma mansoni, affecting millions of people in tropical and subtropical regions. Niclosamide is one of the strategies recommended by the World Health Organization for biological control of snails but it demonstrates high ecotoxicity, motivating the search for new alternatives. Chemoinformatics allows for the understanding and prediction of interactions between molecules and biological targets before experimental synthesis and has been relevant in the prospecting of compounds with molluscicidal potential. Currently there is a gap in the integration between bioassays and prospective results obtained in silico, the consequences of which are the use of larger quantities of compounds and, consequently, higher costs. To evaluate the molluscicidal activity of a naphthoquinone-derived compound on newly hatched B. glabrata snails, obtained from in silico pharmacophoric modeling, snails were exposed in triplicate to concentrations of 3.12 μM, 6.25 μM, 12.5 μM, 25 μM, and 50 μM of the chemical, along with two negative control groups: water and 1% DMSO (DimethylSulfoxide - C2H6OS molecular formula). Snail mortality was monitored daily for 96 hours using a microscope with a camera and LAS EZ software, statistical analysis were performed using the Vegan package of the R Project software.

One-tailed analysis of variance (ANOVA) was used to verify the differences in mortality rates of B. glabrata snails exposed to the compound and the controls. LC50 values and their confidence intervals were obtained by regression analysis using the Probit method. The results obtained demonstrated the compound's promising molluscicidal capacity, showing a cumulative effect and a final LC50 of 7.1 μM, demonstrating the viability of conducting further tests with adult snails based on these results. Based on this study, it was possible to establish laboratory parameters for bioassays with molecules prospected in silico using newly hatched snails as an experimental model for laboratory optimization.