INHIBITORS OF FILARIAL GAMMA-GLUTAMYL CYCLE ENZYMES AS POSSIBLE MACROFILARICIDAL AGENTS

The sensitivity of two γ-glutamyl cycle enzymes i.e. glutamate cysteine ligase (GCL) and γ-glutamyl transpeptidase (γ-GT) from bovine filarial worms Setaria cervi and their counterparts from mammalian liver to known inhibitors i.e. buthionine sulfoximine vs. GCL and serine-borate vs. γ-GT were compared. Two chemical classes i.e. diglycosylated diaminoalkanes (DGDA) and coumarins were studied for their inhibition against filarial GCL, glutathione synthetase (GS) and γ-GT and the most effective inhibitors of filarial enzymes were also looked for their effect on GSH levels of bovine filariae S. cervi in vitro. Results revealed some definite correlation between the enzyme inhibition with GSH depletion in S. cervi females by certain DGDA and coumarin derivatives.