{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:50:11Z","timestamp":1770335411201,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T00:00:00Z","timestamp":1529366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is an infectious disease mainly associated with poverty that affects millions of people worldwide. Since treatment for this disease relies only on the use of praziquantel, there is an urgent need to identify new antischistosomal drugs. Piplartine is an amide alkaloid found in several Piper species (Piperaceae) that exhibits antischistosomal properties. The aim of this study was to evaluate the structure\u2013function relationship between piplartine and its five synthetic analogues (19A, 1G, 1M, 14B and 6B) against Schistosoma mansoni adult worms, as well as its cytotoxicity to mammalian cells using murine fibroblast (NIH-3T3) and BALB\/cN macrophage (J774A.1) cell lines. In addition, density functional theory calculations and in silico analysis were used to predict physicochemical and toxicity parameters. Bioassays revealed that piplartine is active against S. mansoni at low concentrations (5\u201310 \u00b5M), but its analogues did not. In contrast, based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, piplartine exhibited toxicity in mammalian cells at 785 \u00b5M, while its analogues 19A and 6B did not reduce cell viability at the same concentrations. This study demonstrated that piplartine analogues showed less activity against S. mansoni but presented lower toxicity than piplartine.<\/jats:p>","DOI":"10.3390\/ijms19061802","type":"journal-article","created":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T11:20:36Z","timestamp":1529407236000},"page":"1802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Structure\u2013Activity Relationship of Piplartine and Synthetic Analogues against Schistosoma mansoni and Cytotoxicity to Mammalian Cells"],"prefix":"10.3390","volume":"19","author":[{"given":"Yuri","family":"Campelo","sequence":"first","affiliation":[{"name":"N\u00facleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Universidade Federal do Piau\u00ed, UFPI, Parna\u00edba-PI, 64202-020 Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia, RENORBIO, Ponto focal Universidade Federal do Piau\u00ed, UFPI, Teresina, PI, 64049-550, Brazil"},{"name":"Instituto de Educa\u00e7\u00e3o Superior do Vale do Parna\u00edba, FAHESP\/IESVAP, Parna\u00edba-PI, 64212-790, Brazil"}]},{"given":"Alicia","family":"Ombredane","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Nanobiotecnologia, Instituto de Biologia, Campus Darcy Ribeiro, Universidade de Bras\u00edlia, UnB, Bras\u00edlia-DF 70910-900, Brazil"}]},{"given":"Andreanne","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"\u00c1rea de Morfologia, Faculdade de Medicina, Universidade de Bras\u00edlia, UnB, Bras\u00edlia-DF 70910-900, Brazil"}]},{"given":"Lucas","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Laboratorio de Imunologia, Faculdade de Medicina, Universidade de Bras\u00edlia, UnB, Bras\u00edlia-DF 70910-900, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1961-7281","authenticated-orcid":false,"given":"Daniel","family":"Moreira","sequence":"additional","affiliation":[{"name":"\u00c1rea de Morfologia, Faculdade de Medicina, Universidade de Bras\u00edlia, UnB, Bras\u00edlia-DF 70910-900, Brazil"}]},{"given":"Alexandra","family":"Pl\u00e1cido","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, GRAQ, Instituto Superior de Engenha do Porto, ISEP, Porto 4200-072, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6619-2293","authenticated-orcid":false,"given":"Jefferson","family":"Rocha","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia, RENORBIO, Ponto focal Universidade Federal do Piau\u00ed, UFPI, Teresina, PI, 64049-550, Brazil"}]},{"given":"Harold","family":"Hilarion Fokoue","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas, Universidade Federal do Rio de Janeiro, CCS, Cidade Universit\u00e1ria, Rio de Janeiro-RJ 21941-902, Brasil"}]},{"given":"Lydia","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Universidade de S\u00e3o Paulo, S\u00e3o Paulo-SP 01005-010, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9679-6079","authenticated-orcid":false,"given":"Ana","family":"Mafud","sequence":"additional","affiliation":[{"name":"Instituto de F\u00edsica de S\u00e3o Carlos, Universidade de S\u00e3o Paulo-SP 01005-010, Brazil"}]},{"given":"Yvonne","family":"Mascarenhas","sequence":"additional","affiliation":[{"name":"Instituto de F\u00edsica de S\u00e3o Carlos, Universidade de S\u00e3o Paulo-SP 01005-010, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-3398","authenticated-orcid":false,"given":"Cristina","family":"Delerue-Matos","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, GRAQ, Instituto Superior de Engenha do Porto, ISEP, Porto 4200-072, Portugal"}]},{"given":"Tatiana","family":"Borges","sequence":"additional","affiliation":[{"name":"Laboratorio de Imunologia, Faculdade de Medicina, Universidade de Bras\u00edlia, UnB, Bras\u00edlia-DF 70910-900, Brazil"}]},{"given":"Graziella","family":"Joanitti","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Nanobiotecnologia, Instituto de Biologia, Campus Darcy Ribeiro, Universidade de Bras\u00edlia, UnB, Bras\u00edlia-DF 70910-900, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-2744","authenticated-orcid":false,"given":"Daniel","family":"Arcanjo","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Plantas Medicinais, NPPM, Universidade Federal do Piau\u00ed, UFPI, Parna\u00edba-PI 64202-020, Brazil"}]},{"given":"Massuo","family":"Kato","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Universidade de S\u00e3o Paulo, S\u00e3o Paulo-SP 01005-010, Brazil"}]},{"given":"Selma","family":"Kuckelhaus","sequence":"additional","affiliation":[{"name":"\u00c1rea de Morfologia, Faculdade de Medicina, Universidade de Bras\u00edlia, UnB, Bras\u00edlia-DF 70910-900, Brazil"}]},{"given":"Marcos","family":"Silva","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisa em Doen\u00e7as Negligenciadas, Universidade de Guarulhos, Guarulhos-SP 07023-070, Brazil"}]},{"given":"Josu\u00e9","family":"De Moraes","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisa em Doen\u00e7as Negligenciadas, Universidade de Guarulhos, Guarulhos-SP 07023-070, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1096-3236","authenticated-orcid":false,"given":"Jos\u00e9","family":"Leite","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Universidade Federal do Piau\u00ed, UFPI, Parna\u00edba-PI, 64202-020 Brazil"},{"name":"\u00c1rea de Morfologia, Faculdade de Medicina, Universidade de Bras\u00edlia, UnB, Bras\u00edlia-DF 70910-900, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,19]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2016). 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