Central idea: The Kolkata-based Indian Association for the Cultivation of Science (IACS) have established the potential of quinoline derivatives to treat drug-resistant leishmaniasis, which is also called kala-azar or black fever.

What is Kala Azar?

• Kala-Azar is a vector-borne (sandfly) neglected tropical disease caused by the protozoan parasites of the genus leishmania.
• It afflicts the world’s poorest populations in over 90 countries throughout Asia, Africa, the Middle East, and Central and South America.
• Current annual estimates of kala-azar are about 1,00,000.
• More than 95% of cases reported to the WHO are from India and other tropical countries, most importantly co-infection with HIV, which leads to an immunocompromised state.

How does Quinoline work over this?

• The quinoline derivative is a potent inhibitor of an enzyme called topoisomerase 1 (LdTop1).
• This enzyme is essential for the maintenance of DNA architecture in parasites and is distinct from the one found in humans.
• Poisoning LdTop1 imparts significant cytotoxicity to both Leishmania parasites found in the gut of sandfly vectors (promastigotes) and those found in infected humans (amastigotes) of both the wild type and the antimony-resistant isolates.
• This is done without inducing lethality to human and mice host cells.

Significance of quinoline treatment

• Overcoming drug resistance in clinical leishmaniasis is a severe challenge in rural India.
• The current treatment regimens against kala-azar use formulations that are toxic and induce high levels of drug-resistance.

What is the breakthrough?

• The novel inhibitor targeting the leishmania parasites was identified by screening them against recombinant Leishmania topoisomerase 1 enzyme.
• In all, 21 derivatives were prepared and evaluated for their antileishmanial activity, and one of them was found to be effective.

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