In Vitro and In Vivo Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from Drimys brasiliensis Branches

Autor(es)

Umehara, Eric ; Cajas, Rayssa A. ; Conceicao, Gabriel B. ; Antar, Guilherme M. ; Andricopulo, Adriano D. ; de Moraes, Josue ; Lago, Joao Henrique G.

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 30, n. 2, p. 11-pg., 2025-01-01.

Resumo

In the present study, the hexane extract from branches of Drimys brasiliensis (Winteraceae) displayed potent activity against Schistosoma mansoni parasites (100% mortality of the worms at 200 mu g/mL). Bioactivity-guided fractionation afforded, in addition to the previously reported bioactive sesquiterpene 3,6-epidioxy-bisabola-1,10-diene, two chemically related drimane sesquiterpenes-polygodial (1) and 9-deoxymuzigadial (2). The anti-S. mansoni effects for compounds 1 and 2 were determined in vitro, with compound 1 demonstrating significant potency (EC50 value of 10 mu M for both male and female worms), while 2 was inactive. Cytotoxicity assays against Vero cells revealed no toxicity for either compound (CC50 > 200 mu M). Additionally, an in silico analysis was conducted using the SwissADME platform for 1, revealing that this natural sesquiterpene exhibited adherence to several ADME parameters and no PAINS violations. Finally, in vivo studies with S. mansoni-infected mice treated with compound 1 demonstrated a 44.0% reduction in worm burden, accompanied by decreases in egg production of 71.8% in feces and 69.5% in intestines. These findings highlight the potential of polygodial (1) as a promising prototype for schistosomiasis treatment. (AU)

• Processo FAPESP: 23/08418-6 - Busca de metabólitos bioativos oriundos da biodiversidade brasileira como candidatos a fármacos para doenças causadas por helmintos
• Beneficiário: Josué de Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 23/12447-1 - Busca de metabólitos especializados oriundos da biodiversidade florística brasileira como candidatos a fármacos para doenças tropicais negligenciadas
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular
• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs