Anthelmintic activity of a nanoformulation based on thiophenes identified in Tagetes patula L. (Asteraceae) against the small ruminant nematode Haemonchus contortus

Autor(es)

Politi, Flavio Augusto Sanches ^[1] ; Bueno, Renata Vieira ^[2] ; Zeoly, Lucas Andre ^[3] ; Fantatto, Rafaela Regina ^[1] ; Eloy, Josimar de Oliveira ^[4] ; Chorilli, Marlus ^[1] ; Coelho, Fernando ^[3] ; Guido, Rafael Victorio Carvalho ^[2] ; Chagas, Ana Carolina de Souza ^[5] ; Furlan, Maysa ^[6]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Araraquara, SP - Brazil

^[2] Univ Sao Paulo, Phys Inst Sao Carlos IFSC, Sao Carlos, SP - Brazil

^[3] Univ Campinas UNICAMP, Chem Inst, Campinas, SP - Brazil

^[4] Fed Univ Ceara UFC, Coll Pharm Dent & Nursing, Fortaleza, Ceara - Brazil

^[5] Brazilian Agr Res Corp Embrapa, Sao Carlos, SP - Brazil

^[6] Sao Paulo State Univ UNESP, Chem Inst, Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Acta Tropica; v. 219, JUL 2021.
• Citações Web of Science: 0

Resumo

The synthesis of thiophenic compounds, previously identified in Tagetes patula, revealed that 4-(5 `-(hydroxymethyl)-{[}2,2 `-bithiophene]-5-yl)but-3-yn-1-ol), or simply Thio1, has a pronounced in vitro anthelmintic effect against Haemonchus contortus, showing 100% efficacy in the egg hatch and larval development tests presenting EC50 = 0.1731 mg.mL-1 and EC50 = 0.3243 mg.mL-1, respectively. So, this compound was selected to preparation of a nanostructured formulation to be orally administered to Santa Ine<SIC>s sheep. In general, from the fecal egg count reduction test (FECRT), it was observed that the product kept the parasitic load in the digestive tract of the hosts stable, with eggs per gram of faeces (EPG) counts having a mean value < 3,000 (EPGmean = 2167.1, efficacy = 36,45%), thus protecting the animals from health risks caused by a massive nematode infestation. To better understand the mode of action of this thiophene derivative, in silico molecular modeling studies were carried out with the glutamate-activated chloride channel (GluCl), a well-known molecular target of anthelmintic compounds. Based on the affinity score (GlideScore = -5.7 kcal.mol-1) and the proposed binding mode, Thio1 could be classified as a potential GluCl ligand, justifying the promising results observed in the anthelmintic assays. (AU)

• Processo FAPESP: 14/50926-0 - INCT 2014: biodiversidade e produtos naturais
• Beneficiário: Vanderlan da Silva Bolzani
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 13/04737-8 - Descoberta e Planejamento de Inibidores da Síntese de Folatos como Candidatos a Defensivos Agrícolas para a Cultura da Cana-de-Açúcar
• Beneficiário: Renata Vieira Bueno
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/03493-8 - Potencial de extratos brutos, óleo essencial e compostos isolados obtidos de Tagetes patula L. (Asteraceae) como antiparasitário botânico contra Rhipicephalus (Boophilus) microplus, Haemonchus contortus e Cimex lectularis
• Beneficiário: Flávio Augusto Sanches Politi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/08042-9 - Descoberta e planejamento de novos agentes antibacterianos candidatos a defensivos agrícolas para a cultura da cana-de-açúcar: triagem biológica, química medicinal e biologia estrutural
• Beneficiário: Rafael Victorio Carvalho Guido
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOEN - Jovens Pesquisadores