15β-Senecioyl-oxy-ent-kaur-16-en-19-oic Acid, a Diterpene Isolated from Baccharis lateralis, as Promising Oral Compound for the Treatment of Schistosomiasis

Abstract

Praziquantel is the only available drug to treat schistosomiasis, and therefore, urgent studies must be performed to identify new anthelmintic agents. This study reports the anthelmintic evaluation of two related ent-kaurane diterpenes isolated from aerial parts of Baccharis lateralis (Asteraceae), entkaur-16-en-19-oic acid (1) and 15β-senecioyl-oxy-ent-kaur-16-en-19oic acid (2) against Schistosoma mansoni in vitro and in a murine model of schistosomiasis. Both compounds exhibited in vitro activity with lethal concentration 50% (LC 50 ) values of 26.1 μM (1) and 11.6 μM (2) as well as reduced toxicity against human cell lines, revealing a good selectivity profile, mainly with compound 2 (selectivity index > 10). Compound 2 also decreased egg production and caused morphological alterations in the parasite reproductive system. In mice infected with S. mansoni, oral treatment with compound 2 at 400 mg/kg, the standard dose used in this model of schistosomiasis, caused a significant reduction in a total worm burden of 61.9% (P < 0.01). S. mansoni egg production, a key mechanism for both transmission and pathogenesis, was also markedly reduced. In addition, compound 2 achieved a significant reduction in hepatosplenomegaly. Therefore, the diterpene 15β-senecioyl-oxy-ent-kaur-16-en-19-oic acid (2) has an acceptable cytotoxicity profile and is orally active in a murine schistosomiasis model.

Evaluation of Gibbilimbol B, Isolated from Piper malacophyllum (Piperaceae), as an Antischistosomal Agent

“…In this study, the SI values calculated were >192.3, demonstrating a highly selective anthelmintic effect. Comparatively, this high SI values exceeded those obtained for other relevant natural products with antischistosomal properties [12,35,36] . The low potential cytotoxic of gibbilimbol B has been previously described [28,37] .…”

Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

“…Thus, our data suggest that amiodarone should have antischistosomal properties under its current antiarrhythmic drug regimen. Although the amiodarone is commonly used in clinical practice, the risk of adverse effects acts as a limiting factor to its utilization [34][35][36][37][38][39][40][41][42][43][44][45][46][47]. As community-wide treatment would be expected at least in most endemic areas for schistosomiasis, this would be a problem.…”

“…An in vitro primary screening against adult schistosomes was performed as previously described [ 35 , 36 ]. Briefly, adult parasites were collected from the portal system and mesenteric veins of infected mice 7 weeks post-infection (parasite ex vivo).…”

Protein Kinases: Potential Drug Targets Against Schistosoma japonicum

“…However, certain experiments are still needed to prove the specific efficacy of artemisinin. Recent studies have discovered some novel drugs such as antimalarial quinoxaline derivative (MMV007204), N,N’-Diarylurea MMV665852 analogs and 15β-senecioyl-oxy-ent-kaur-16 -en-19-oic acid, but their efficacy are not superior to PZQ ( Cowan et al., 2015 ; Sessa et al., 2020 ; Debbert et al., 2021 ). Therefore, it is of great significance to develop novel and affordable anti-schistosomiasis drugs that are structurally and functionally different from PZQ in order to tackle the rapid development of PZQ resistance.…”