Fungal Transformation and Schistosomicidal Effects of Pimaradienoic Acid

Abstract

The schistosomicidal effects of pimaradienoic acid (PA) and two derivatives, obtained by fungal transformation in the presence of Aspergillus ochraceus, were investigated. PA was the only compound with antischistosomal activity among the three diterpenes studied, with the ability to significantly reduce the viability of the parasites at concentrations ranging from 25 to 100 μM. PA also promoted morphological alterations of the tegument of Schistosoma mansoni, separated all the worm couples, and affected the production and development of eggs. Moreover, this compound was devoid of toxicity toward human fibroblasts. In a preliminary in vivo experiment, PA at a dose of 100 mg/kg significantly diminished the number of parasites in infected Balb/c mice. Taken together, these results show that PA may be potentially employed in the discovery of novel schistosomicidal agents, and that diterpenes are an important class of natural compounds for the investigation of agents capable of fighting the parasite responsible for human schistosomiasis.

Diterpenes as lead molecules against neglected tropical diseases

“…In the latter case, the parasiticidal effect of the organism was thought to be exerted through protein metabolism. Pimaradienoic acid and two derivatives from Aspergillus ochraceus exhibited promising anti‐ S. mansoni activity at 25 to 100 μM (Porto et al ., ). A similar activity was also observed when S. mansoni was treated with phytol in 50 to 100 µg/mL (de Moraes et al ., ).…”

Natural Products as Leads in Schistosome Drug Discovery

“…An in vitro study with pimaradienoic acid ( 6 ), a major diterpene isolated from Viguiera arenaria , promoted morphological alterations of the S. mansoni tegument and caused the separation of 100% of the coupled adult worms into individual male and female worms at a concentration of 100 µM after 24 h of exposure, thus justifying the absence of egg production at this concentration [ 66 ]. A preliminary in vivo study with experimentally infected mice also indicated that, at a dose of 100 mg/kg/day, compound 6 reduced the total number of adult S. mansoni worms by about 40%.…”

“…A preliminary in vivo study with experimentally infected mice also indicated that, at a dose of 100 mg/kg/day, compound 6 reduced the total number of adult S. mansoni worms by about 40%. Moreover, compound 6 was devoid of in vitro cytotoxicity against a human fibroblast cell line at a broad concentration range (7.8–500 µM), indicating its selectivity [ 66 ].…”

Schistosomicidal Activity of Dihydrobenzofuran Neolignans

“…mansoni worms. [ ][ ][ ] Here, we observed that the active compounds significantly affected both female and male worms.…”