Type II DNA topoisomerases in trypanosomatid and apicomplexan parasites.

Somenath Roy Chowdhury, Arpita Bhoumik, Vivek Kumar Gupta, Hemanta K Majumder

Acta tropica 2022 Oct

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Diseases caused by trypanosomatid parasites have no commercially available vaccines for human application. Treatment modalities completely rely on chemotherapeutics strategies that often exhibit clinical drawbacks, like host toxicity, side effects and treatment failure for drug resistance. These, in many instances, are costly, making them unaffordable for certain groups of beneficiaries. To find reasonable solutions, researchers are attempting to identify and validate new drug targets that would offer parasite specificity. DNA topoisomerases in parasites present a consolidated class of drug targets due to their multiple structural and functional differences with host homologs. Type II DNA topoisomerases in these parasites, in particular, have been attracting interest of scientific community attributable to their pivotal role in the replication of the atypical DNA. In this article, we present a detailed review of structural and functional features of type II DNA topoisomerases of clinically-relevant trypanosomatid and apicomplexan parasites. Also, we provide up-to-date information on different molecules that target these enzymes. Altogether, the review will largely help in understanding the rationale for exploiting type II DNA topoisomerases in these groups of parasites as drug targets. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Somenath Roy Chowdhury, Arpita Bhoumik, Vivek Kumar Gupta, Hemanta K Majumder. Type II DNA topoisomerases in trypanosomatid and apicomplexan parasites. Acta tropica. 2022 Oct;234:106613