Schistosomicidal activity of kaurane, labdane and clerodane-type diterpenes obtained by fungal transformation

Schistosomiasis continues to be a huge challenge for researchers, pharmaceutical companies, and governments in developing countries. Diterpene compounds are good source for the development of novel potential leading compounds to treat schistosomiasis. We are reporting herein the schistosomicidal activity of ent-kaurenoic acid, ent-copalic acid, ent-hardwickiic acid, isolated from oleoresins of Copaifera spp, and of their derivatives obtained by fungal transformation with strains of Aspergillus fumigants, A. terreus, A. phoenicis and A. ochraceus, and of Cunninghamella echinulata e C. elegans. The in vitro antiparasitical assays were performed using adult worm pairs of Schistosoma mansoni for the evaluation of the worm pairing, egg production, and eggs development. Ten kaurane, labdane and clerodane-type diterpenes were obtained by fungal transformation and 7 alpha-acetoxy-ent-kaur-16-en-19-oic acid and ent-hardwickiic acid were the most active ones by causing mortality of 100 % of the parasites within 24 h (concentrations of 100.0 and 200.0 mu M) and displaying respective IC50 values for 24, 48 and 72 h of 56.7, 37.6 and 29.2 mu M and 29.6, 30.8 and 25.7 mu M. Additionally, 7a-acetoxy-em-kaur-16-en-19-oic acid and ent-hardwickiic acid highly reduced the number of laid eggs at 6.25 and 12.5 mu M, respectively. These diterpenes should be further investigated as potential candidates for antiparasitic drug discovery. (AU)