Topoisomerase 1B as a target against leishmaniasis

Mini Reviews in Medicinal Chemistry
Ilda D'AnnessaAlessandro Desideri

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 anti-leishmaniasis 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.

Citations

May 31, 2016·Expert Opinion on Drug Discovery·Joachim Müller, Andrew Hemphill
Aug 18, 2016·Toxicon : Official Journal of the International Society on Toxinology·Danya Bandeira LimaAlice Maria Costa Martins
Sep 19, 2016·European Journal of Medicinal Chemistry·Ana TejeríaFrancisco Palacios
May 19, 2018·Current Medicinal Chemistry·Rosa M RegueraRafael Balaña-Fouce
Mar 1, 2019·Frontiers in Cellular and Infection Microbiology·Jonathan Munera LópezSergio O Angel
Jan 22, 2021·Expert Opinion on Therapeutic Patents·Asier SelasConcepción Alonso

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