Molluscicidal and Schistosomicidal Activities of 2-(1H-Pyrazol-1-yl)-1,3,4-thiadiazole Derivatives

<b>Background/objectives:</b> Schistosomiasis is caused by flatworms of the genus <i>Schistosoma</i>, for which mollusks of the genus <i>Biomphalaria</i> are intermediate hosts. Niclosamide (NCL) is a molluscicide recommended by the World Health Organization (WHO) for control of <i>Biomphalaria</i>. Although effective, it is expensive and environmentally toxic, which raises concerns regarding its widespread use. As a result, we explored new synthetic substances as alternative strategies for controlling <i>Biomphalaria glabrata</i>. We evaluated the molluscicidal activity of 2-(1<b><i>H</i></b>-py-razol-1-<b><i>yl</i></b>)-1,3,4-thiadiazole and 2-(4,5-dihydro-1<b><i>H</i></b>-pyrazol-1-<b><i>yl</i></b>)-1,3,4-thiadiazole derivatives against <i>B. glabrata</i> snails and embryos, as well as <i>Schistosoma</i> cercariae (infective larvae). <b>Methods:</b> Adult and young snails were added to 24-well plates containing 20 synthetic compounds from the PDAN series for initial screening over 96 h at a concentration of 100 ppm. Water and NCL (2 ppm) were used as the negative and positive controls, respectively. Active compounds in the adult <i>B. glabrata</i> assay were selected for the tests vs. embryos and cercariae. <b>Results:</b> In the initial screen, only PDAN 52 (63 ± 4%) and 79 (12 ± 3%) showed molluscicidal activity at a concentration of 100 ppm up to 48 h. Consequently, we selected only PDAN 52. The LC₅₀ value found in the tests on embryos after 24 h of treatment was 20 ± 2 ppm and, after 48 h, it was 4 ± 0.5 ppm. Against cercariae, we measured an LC₅₀ value of 68 ± 5 ppm after 4 h of treatment. PDAN 52 did not induce marked toxicity against a second mollusk, <i>Physella acuta</i>, after 48 h of exposure. <b>Conclusions:</b> We highlight the promising molluscicidal activity of PDAN 52 against different developmental stages of the mollusk, <i>B. glabrata</i>, as well the infective larvae of <i>Schistosoma mansoni</i>.