Cancer drugs for leishmaniasis
doi:10.1038/nindia.2011.40 Published online 21 March 2011
Two widely used anti-cancer drugs — doxorubicin and mitomycin C — may well have the potential to become the next cure for leishmaniasis, a parasitic disease affecting millions in developing countries.
Researchers from the Indian Institute of Technology, Guwahati found in lab studies that the drugs killed the leishmania parasites by inhibiting the activity of trypanothione reductase (TryR), the enzyme necessary for the survival of the parasite in host cells.
Existing drugs to combat the leishmania parasite are expensive and low on efficacy. Besides, they show severe side effects. All this prompted the search for an alternative therapy. The researchers conducted computer-based simulation studies to look at the interaction of TryR and the drugs. Both drugs bound to the active site of TryR inhibiting its activity.
"These two drugs seem to be potential drug candidates for various types of leishmaniasis including visceral leishmaniasis or Kala-azar," says lead researcher Vikash Kumar Dubey.
The anti-cancer agents are quinine derivatives containing quinone groups. TryR reduces the quinone groups to hydroquinones, which trigger chemical events that lead to accumulation of superoxide free radicals, a type of reactive oxygen species, inside the parasite cells. This generation of free radicals paves the controlled death of parasites.
Tested on human red blood cells, the drugs were found to be nontoxic in limited dose. Earlier studies found doxorubicin to have mild toxicity on heart. However, liposome encapsulation of doxorubicin is highly efficient in increasing its therapeutic value with no toxicity on heart. "A liposome-encapsulated doxorubicin appears to be a better anti-leishmanial agent," Dubey says.
- Shukla, A. K. et al. Evaluation of selected antitumor agents as subversive substrate and potential inhibitor of trypanothione reductase: an alternative approach for chemotherapy of leishmaniasis. Mol. Cell. Biochem. doi: 10.1007/s11010-011-0762-0 (2011)