Title:Topoisomerase 1B as a Target Against Leishmaniasis
Volume: 15
Issue: 3
Author(s): Ilda D’Annessa, Silvia Castelli and Alessandro Desideri
Affiliation:
Keywords:
Anti-leishmanial drugs, Drug development, Leishmaniasis, Parasitic infections, Protozoa, Topoisomerase 1B.
Abstract: Leishmaniasis affects more than 12 million people in 98 countries, the infection being
caused by more than 20 species of protozoan parasites belonging to the genus Leishmania and spread
by sandflies bite. Poor sanitary conditions, malnutrition, deforestation and urbanization increase the
risk for leishmaniasis. Leishmaniasis is the only tropical disease treated with non-anti-leishmanial
drugs, among which liposomal amphotericin B, a combination of pentavalent antimonials and
paromomycin and miltefosine, that are highly toxic, represent the most used ones. Drug resistance is
now widespread and the search for new molecular targets is open. Topoisomerase 1B, that controls the
topological state of DNA and is essential for the parasites viability, has been detected as a promising target for antileishmaniasis
therapy. The enzyme presents structural/functional differences with the human counterpart, making it
unique among Eukarya. Here we review the structural features of this enzyme and the drugs that can be developed and
used for this specific targeting.