The Indian Association for the Cultivation of Science (IACS) in Kolkata has demonstrated the potential of quinoline derivatives to treat drug-resistant leishmaniasis, also known as kala-azar or black fever.
What exactly is Kala Azar?
- Kala-Azar is a neglected tropical illness transmitted by sandflies and caused by protozoan parasites of the genus Leishmania.
- It affects the world’s poorest people in more than 90 nations across Asia, Africa, the Middle East, Central and South America.
- The current annual projection of kala-azar is around 100,000.
- More than 95% of cases reported to the WHO are from India and other tropical nations, with the most common cause being HIV co-infection, which results in immunocompromised status.
How does Quinoline work over this?
- The quinoline derivative is an effective suppressor of the enzyme topoisomerase 1. (LdTop1).
- This enzyme, which differs from the one present in humans, is required for the maintenance of DNA architecture in parasites.
- Poisoning LdTop1 causes significant cytotoxicity in both the wild type and antimony-resistant Leishmania parasites found in the guts of sandfly vectors (promastigotes) and in infected people (amastigotes).
- This is accomplished without causing death in human or mouse host cells.
The Importance of Quinoline Treatment
- In rural India, overcoming drug resistance in clinical leishmaniasis is a major problem.
- Current kala-azar treatment methods employ toxic formulations that cause high amounts of drug resistance.
What exactly is the breakthrough?
- The new leishmania parasite inhibitor was discovered by screening them against recombinant Leishmania topoisomerase 1 enzyme.
- In total, 21 derivatives were made and tested for antileishmanial activity, with one of them proving effective.
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530401/