Glutathione metabolism of filarial worms: A vulnerable target for the design and synthesis of new antifilarial agents.
The main problem regarding the chemotherapy of filariasis is that no safe and effective drug is available yet to combat the adult human filarial worms. One of the main reasons is the prolonged existence, i.e. survival of filarial worms in mammalian hosts for many years, and having a very strong antioxidant system. Glutathione (GSH) has been identified as an important part of the antioxidant system of many, if not all, living cells and, together with glutathione reductase (GR), it maintains the correct intracellular redox balance. It protects the cell against oxidative damage by non-enzymatic scavenging of free radicals and by enzymatic neutralization of toxic hydrogen peroxide, lipid hydroperoxides, and derivatives by glutathione-dependent peroxidases (GPXs) and glutathione-S-transferases (GSTs). Work in this direction reveals that filarial worms can synthesize and recycle GSH, and its depletion may be useful in chemotherapeutic situations in which the cells to be killed and the cells to be spared have substantially different quantitative requirements for GSH. All normal mammalian cells have a considerable amount of GSH, whereas filarial worms may have GSH concentrations close to that required for their survival and, therefore, a little manipulation of the glutathione metabolism of filarial worms may have drastic consequences. The present review details the application of the glutathione metabolism of filarial worms as a target for the design and synthesis of new antifilarial agents.
Gupta
Sapna
S
Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
Srivastava
Arvind Kumar
AK
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005368:Filariasis / Q000188:drug therapy*; D005369:Filaricides / Q000138:chemical synthesis / Q000737:chemistry*; D005370:Filarioidea / Q000201:enzymology* / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008954:Models, Biological
D000975:Antioxidants; D005369:Filaricides; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione