Antidote for leishmaniasis
doi:10.1038/nindia.2010.100 Published online 28 July 2010
New research has identified several organic compounds that could inhibit the growth of Leishmania parasites, known to cause leishmaniasis in humans. Guided by a computer-aided drug design system, the research has shown that the organic compounds block the activity of an enzyme that is key to the survival of these parasites in the host.
The study may help the development of drugs against leishmaniasis, which claims around 500,000 to 1 million lives every year across the globe. Existing therapies for leishmaniasis are toxic to humans and have also resulted in the emergence of drug-resistant parasitic strains.
The researchers studied a potential drug development target trypanothione reductase (TryR), an enzyme that helps the metabolic activities of the parasite for its survival in the host. TryR has ealier been successful in drug design studies on Trypanosoma cruzi, a parasite that causes Chagas disease.
The researchers chose to target TryR of Leishmania infantum and tested the inhibitory activities of three types of trycyclic organic compounds. They found that all the compounds bind to the active site of the enzyme through the formation of hydrogen bonds. The modelled binding modes provide an insight into the interactions of these compounds with the enzyme, and thus could be used for the design and synthesis of specific inhibitors.
"Because TryR is unique in the Leishmania parasite and is not found in the mammalian host, these TryR-targeted compounds may be exploited to yield safe, affordable drugs," says lead researcher Vikash Kumar Dubey.
- Kannan, S. et al. Molecular docking studies of selected tricyclic and quinone derivatives on trypanothione reductase of_Leishmania infantum_. J. Comput. Chem. 31, 2463–2475 (2010)