Depletion of Intracellular Glutathione of Setaria cervi by Buthionine sulfoximine, Carmustine and their analogues

摘要

A majority if not all, the normal mammalian tissues have a large excess of glutathione (GSH) compared to filarial parasites that invade them have levels close to that required for survival. Glutathione protects the filarial organisms against attack by host generated free radicals. Therefore, depletion of filarial intracellular GSH levels by antifilarial agents may be more harmful to parasites than to the normal tissues of the host organisms. Buthionine sulfoximine (BSO) and Carmustine (BCNU) are the known mammalian GSH depletors. However, their effect on filariids particularly the bovine ones is largely unknown which may provide leads for the synthesis of this class of antifilarial drugs. With this aim the effect of BSO and BCNU on intracellular glutathione content (GSH) of bovine filariids Setaria cervi was investigated. GSH depletion potential of BSO and BCNU was investigated at different concentrations ranging from micro to millimoles during 6 h incubation period. In each case there was found an increase in per cent decline of intracellular GSH of S.cervi with increasing concentration of the inhibitors. Several analogues of BSO and BCNU synthesized at CDRI, Lucknow, have been evaluated for their antifilarial efficacy as well as on their capability to deplete intracellular GSH in filariids. N~1, N~n -diglycosylated diaminoalkanes and trimethyl coumarin analogues were observed the best and have a promising future in the design and synthesis of new class of antifilarial drugs.