Characterizing the Bi-Subunit Type IB DNA Topoisomerase of Leishmania Parasites; a Novel Scenario for Drug Intervention in Trypanosomatids

Rosa   M.   Reguera; Rosario      Diaz-Gonzalez; Yolanda      Perez-Pertejo; Rafael      Balana-Fouce

doi:10.2174/138945008786786118

Abstract

African and South American trypanosomes and leishmanias are unicellular protozoan parasites, forming part of the order Kinetoplastida. These ancient eukaryotes are causative agents of some of the most devastating neglected Tropical Diseases called trypanosomiasis and leishmaniasis. Despite the efforts to develop effective vaccines, immunoprophylaxis is not even a method of prevention of these diseases at present. Current antiprotozoal chemotherapy is often expensive, has side or toxic effects and it does not provide economic profits to the Pharmaceuticals, which have scant enthusiasm in R + D investments in this field. The surprising finding of unusual bi-subunit type IB DNA-topoisomerase in kinetoplastids adds a new promising drug target to antiprotozoal chemotherapy. The remarkable differences between trypanosomal and leishmanial DNA-topoisomerase IB with respect to the one in the mammalian hosts, have provided a new lead in the study of structural determinants that can be effectively targeted. This review provides an update on recent progress in research in kinetoplastids topoisomerase IB as potential chemotherapeutic target against this group of parasitic diseases.

Keywords: DNA topoisomerase IB, camptothecin, parasitic protozoa, Leishmania, trypanosomatids, Tropical diseases

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