DNA Topoisomerase as Drug Target in unicellular protozoan parasite Leishmania donovani

Abstract

Visceral leishmaniasis or Kala-Azar is a neglected tropical disease caused by the unicellular kinetoplastid parasite Leishmania donovani.
The treatments available have various shortcomings like toxicity and high cost. The development of resistance in the strains makes the
treatment less effective. Hence, there is a need for new and better treatments. DNA topoisomerases are a group of enzymes present
ubiquitously in all organisms from unicellular protozoan parasites to humans. These enzymes control the cell's topological problems
caused by DNA double helix during nucleic acid metabolism. However, the leishmanial topoisomerase (LdTOPILS) is very different
from the human topoisomerase in structure, expression, and function. Therefore, LdTOPILS acts as a potent target for newer drugs. A
diverse range of compounds has been developed to date against Leishmanial topoisomerases. This review article describes Leishmania
topoisomerase enzyme's structural and catalytic activity and Topo-targeted antileishmanial drug development. Therefore, this review
article would be beneficial for researchers to understand the structure-function relationship of topoisomerases with their targeted
inhibitors.