Targeting polyamine metabolism for finding new drugs against leishmaniasis: a review

Mini Reviews in Medicinal Chemistry
Andrea IlariGianni Colotti

Abstract

Leishmaniasis is a neglected disease affecting more than 12 million people worldwide. The most used drugs are pentavalent antimonials that are very toxic and display the problem of drug resistance, especially in endemic regions such as Bihar in India. For this reason, it is urgent to find new and less toxic drugs against leishmaniasis. To this end, the understanding of pathways affecting parasite survival is of prime importance for targeted drug discovery. The parasite survival inside the macrophage is strongly dependent on polyamine metabolism. Polyamines are, in fact, very important for cell growth and proliferation. In particular, spermidine (Spd), the final product of the polyamine biosynthesis pathway, serves as a precursor for trypanothione (N1,N8- bis(glutathionyl)spermidine, T(SH)2) and hypusine (N(ε)-(4-amino-2-hydroxybutyl)lysine). T(SH)2 is a key molecule for parasite defense against the hydrogen peroxide produced by macrophages during the infection. Hypusination is a posttranslational modification occurring exclusively in the eukaryotic initiation factor 5A (eIF5A), which has an important role in avoiding the ribosome stalling during the biosynthesis of protein containing polyprolines sequences. The enzymes, belongi...Continue Reading

Citations

Jan 19, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Francesco SaccolitiAndrea Ilari
Aug 24, 2019·Phytotherapy Research : PTR·Pone Kamdem Boniface, Elizabeth Igne Ferreira
Jul 24, 2018·Current Drug Discovery Technologies·Debarshi K MahapatraShovanlal Gayen
May 8, 2018·Infectious Disorders Drug Targets·Abdul Aziz A Bin Dukhyil
Feb 5, 2021·Parasitology·Sajad RashidiPaul Nguewa

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