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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Acta Tropica; v. 219, JUL 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 13/04737-8 - Discovery and Design of Folate Synthesis Inhibitors as Agrochemicals Candidates for Sugar Cane Culture
• Grantee: Renata Vieira Bueno
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/03493-8 - Potential of crude extracts, essential oil and pure compounds obtained from Tagetes patula L. (Asteraceae) as botanical biopesticide against Rhipicephalus (Boophilus) microplus, Haemonchus contortus and Cimex lectularis
• Grantee: Flávio Augusto Sanches Politi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/08042-9 - Discovery and development of new antibacterial agents as agrochemicals for sugarcane cultures: biological screening, medicinal chemistry and structural biology
• Grantee: Rafael Victorio Carvalho Guido
• Support Opportunities: Program for Research on Bioenergy (BIOEN) - Young Investigators Grants