Fungal transformation and schistosomicidal effects of pimaradienoic acid.
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.
Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, SP, Brazil.
Thiago S
TS
Porto
Ademar A
AA
da Silva Filho
Lizandra G
LG
Magalhães
Raquel A
RA
dos Santos
Niege A J C
NA
Furtado
Nilton S
NS
Arakawa
Suraia
S
Said
Dionéia C R
DC
de Oliveira
Luiz E
LE
Gregório
Vanderlei
V
Rodrigues
Rodrigo C S
RC
Veneziani
Sérgio R
SR
Ambrósio
D000818:Animals; D001235:Aspergillus ochraceus / Q000378:metabolism*; D019659:Asteraceae / Q000737:chemistry; D001711:Biotransformation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000254:growth & development; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology; D012556:Schistosomicides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*
D004224:Diterpenes; D010936:Plant Extracts; D012556:Schistosomicides; C008911:pimaric acid