Molluscicidal and Schistosomicidal Activities of 2-(1<i>H</i>-Pyrazol-1-<i>yl</i>)-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)...

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Main Authors: Leonardo da Silva Rangel, Daniel Tadeu Gomes Gonzaga, Ana Cláudia Rodrigues da Silva, Natalia Lindmar von Ranke, Carlos Rangel Rodrigues, José Augusto Albuquerque dos Santos, Nubia Boechat, Keyla Nunes Farias Gomes, Guilherme Pegas Teixeira, Robson Xavier Faria
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Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/3/429
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author Leonardo da Silva Rangel
Daniel Tadeu Gomes Gonzaga
Ana Cláudia Rodrigues da Silva
Natalia Lindmar von Ranke
Carlos Rangel Rodrigues
José Augusto Albuquerque dos Santos
Nubia Boechat
Keyla Nunes Farias Gomes
Guilherme Pegas Teixeira
Robson Xavier Faria
author_facet Leonardo da Silva Rangel
Daniel Tadeu Gomes Gonzaga
Ana Cláudia Rodrigues da Silva
Natalia Lindmar von Ranke
Carlos Rangel Rodrigues
José Augusto Albuquerque dos Santos
Nubia Boechat
Keyla Nunes Farias Gomes
Guilherme Pegas Teixeira
Robson Xavier Faria
author_sort Leonardo da Silva Rangel
collection DOAJ
description <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 LC<sub>50</sub> 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 LC<sub>50</sub> 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>.
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spelling doaj-art-d3dde5d4a6ef42a8945bf57281466b682025-08-20T03:43:29ZengMDPI AGPharmaceuticals1424-82472025-03-0118342910.3390/ph18030429Molluscicidal and Schistosomicidal Activities of 2-(1<i>H</i>-Pyrazol-1-<i>yl</i>)-1,3,4-thiadiazole DerivativesLeonardo da Silva Rangel0Daniel Tadeu Gomes Gonzaga1Ana Cláudia Rodrigues da Silva2Natalia Lindmar von Ranke3Carlos Rangel Rodrigues4José Augusto Albuquerque dos Santos5Nubia Boechat6Keyla Nunes Farias Gomes7Guilherme Pegas Teixeira8Robson Xavier Faria9Laboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, BrazilDepartment of Pharmacy, West Zone Campus, State University of Rio de Janeiro (UERJ), Rio de Janeiro 20550-013, BrazilLaboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, BrazilLaboratory of Molecular Modeling and QSAR (Mod Mol QSAR), Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, BrazilLaboratory of Molecular Modeling and QSAR (Mod Mol QSAR), Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, BrazilLaboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, BrazilLaboratory of Drug Synthesis-LASFAR-Farmanguinhos, Fiocruz 21041-250, BrazilLaboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, BrazilLaboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, BrazilLaboratory for Evaluation and Promotion of Evaluation and Promotion of Environmental Health (LAPSA), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil<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 LC<sub>50</sub> 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 LC<sub>50</sub> 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>.https://www.mdpi.com/1424-8247/18/3/429<i>Biomphalaria glabrata</i>schistosomiasis1,3,4-thiadiazolesynthetic molecules
spellingShingle Leonardo da Silva Rangel
Daniel Tadeu Gomes Gonzaga
Ana Cláudia Rodrigues da Silva
Natalia Lindmar von Ranke
Carlos Rangel Rodrigues
José Augusto Albuquerque dos Santos
Nubia Boechat
Keyla Nunes Farias Gomes
Guilherme Pegas Teixeira
Robson Xavier Faria
Molluscicidal and Schistosomicidal Activities of 2-(1<i>H</i>-Pyrazol-1-<i>yl</i>)-1,3,4-thiadiazole Derivatives
Pharmaceuticals
<i>Biomphalaria glabrata</i>
schistosomiasis
1,3,4-thiadiazole
synthetic molecules
title Molluscicidal and Schistosomicidal Activities of 2-(1<i>H</i>-Pyrazol-1-<i>yl</i>)-1,3,4-thiadiazole Derivatives
title_full Molluscicidal and Schistosomicidal Activities of 2-(1<i>H</i>-Pyrazol-1-<i>yl</i>)-1,3,4-thiadiazole Derivatives
title_fullStr Molluscicidal and Schistosomicidal Activities of 2-(1<i>H</i>-Pyrazol-1-<i>yl</i>)-1,3,4-thiadiazole Derivatives
title_full_unstemmed Molluscicidal and Schistosomicidal Activities of 2-(1<i>H</i>-Pyrazol-1-<i>yl</i>)-1,3,4-thiadiazole Derivatives
title_short Molluscicidal and Schistosomicidal Activities of 2-(1<i>H</i>-Pyrazol-1-<i>yl</i>)-1,3,4-thiadiazole Derivatives
title_sort molluscicidal and schistosomicidal activities of 2 1 i h i pyrazol 1 i yl i 1 3 4 thiadiazole derivatives
topic <i>Biomphalaria glabrata</i>
schistosomiasis
1,3,4-thiadiazole
synthetic molecules
url https://www.mdpi.com/1424-8247/18/3/429
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