Chemotherapy of Schistosomiasis.
Abstract
A formulation for enhancing the bioavailability and chemotherapeutic activity of an antischistosomal nitrovinylfuran has been developed. The structure - antischistosomal activity relationship were investigating using over 100 newly synthesized compounds belonging to a single class, i.e., nitrovinylfurans. Mutagenic and antischistosomal activities have been dissociated from hycanthone by suitable structural terations. IA-3 and IA-4 Oxide, developed under this contract, have been investigated further at WRAMRI and found highly effective in the treatment of primates infected with Schistosoma mansoni. Three metabolites of the most effective and least toxic antischistosomal hycanthone analog have been isolated and identified as the aldehyde, the desethyl aldehyde and the desethyl derivatives. The mutagenic activities of five antischistosomal compounds have been determined and compared with each other. Hycanthone was found to have kg for the highest mutagenic activity. The mutagenic activities of metrifonate, IA-4, oxamniquine and of IA-4 N-oxide were several orders of magnitude lower although schistosomicidal activities were approximately the same. Hence, structural modifications of the hycanthone molecule have reduced markedly mutagenic properties while desired chemotherapeutic activities have been maintained. Genetically transferred resistance to the antischistosomal drug hycanthone can be produced in some strains of Schistosoma mansoni.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 28, 1976
- Accession Number
- ADA043877
Entities
People
- Ernest Bueding
Organizations
- Johns Hopkins University