Molecular Basis for Hycanthone Drug Action in Schistosome Parasites

Publication date: Available online 3 February 2020Source: Molecular and Biochemical ParasitologyAuthor(s): Meghan Guzman, Anastasia Rugel, Reid S. Tarpley, Xiaohang Cao, Stanton F. McHardy, Philip T. LoVerde, Alexander B. TaylorAbstractHycanthone (HYC) is a retired drug formerly used to treat schistosomiasis caused by infection from Schistosoma mansoni and S. haematobium. Resistance to HYC was first observed in S. mansoni laboratory strains and in patients in the 1970s and the use of this drug was subsequently discontinued with the substitution of praziquantel (PZQ) as the single antischistosomal drug in the worldwide formulary. In endemic regions, multiple organizations have partnered with the World Health Organization to deliver PZQ for morbidity control and prevention. While the monotherapy reduces the disease burden, additional drugs are needed to use in combination with PZQ to stay ahead of potential drug resistance. HYC will not be reintroduced into the schistosomiasis drug formulary as a combination drug because it was shown to have adverse properties including mutagenic, teratogenic and carcinogenic activities. Oxamniquine (OXA) was used to treat S. mansoni infection in Brazil during the brief period of HYC use, until the 1990s. Its antischistosomal efficacy has been shown to work through the same mechanism as HYC and it does not possess the undesirable properties linked to HYC. OXA demonstrates cross-resistance in Schistosoma strains with HYC resistance and both are ...
Source: Molecular and Biochemical Parasitology - Category: Parasitology Source Type: research