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SHR Neuro Cancer Cardio Lipid Metab Microb

García-Soriano, JC; de, Lucio, H; Elvira-Blázquez, D; Alcón-Calderón, M; Sanz, Del, Olmo, N; Sánchez-Murcia, PA; Ortega, P; de, la, Mata, FJ; Jiménez-Ruiz, A.
The repertoire of iron superoxide dismutases from Leishmania infantum as targets in the search for therapeutic agents against leishmaniasis.
J Enzyme Inhib Med Chem. 2024; 39(1): 2377586 Doi: 10.1080/14756366.2024.2377586 [OPEN ACCESS]
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Co-authors Med Uni Graz: Sánchez Murcia Pedro Alejandro
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Abstract:: Species of Leishmania and Trypanosoma genera are the causative agents of relevant parasitic diseases. Survival inside their hosts requires the existence of a potent antioxidant enzymatic machinery. Four iron superoxide dismutases have been described in trypanosomatids (FeSODA, FeSODB1, FeSODB2, and FeSODC) that hold a potential as therapeutic targets. Nonetheless, very few studies have been developed that make use of the purified enzymes. Moreover, FeSODC remains uncharacterised in Leishmania. In this work, for the first time, we describe the purification and enzymatic activity of recombinant versions of the four Leishmania FeSOD isoforms and establish an improved strategy for developing inhibitors. We propose a novel parameter [(V*_{cyt. c} - V_{cyt. c})/V_{cyt. c}] which, in contrast to that used in the classical cytochrome c reduction assay, correlates linearly with enzyme concentration. As a proof of concept, we determine the IC₅₀ values of two ruthenium carbosilane metallodendrimers against these isoforms.
Find related publications in this database (using NLM MeSH Indexing): Leishmania infantum - enzymology, drug effects; Dose-Response Relationship, Drug - administration & dosage; Structure-Activity Relationship - administration & dosage; Molecular Structure - administration & dosage; Superoxide Dismutase - metabolism, antagonists & inhibitors, chemistry; Antiprotozoal Agents - pharmacology, chemistry, chemical synthesis; Parasitic Sensitivity Tests - administration & dosage; Enzyme Inhibitors - pharmacology, chemistry, chemical synthesis; Leishmaniasis - drug therapy, parasitology
Find related publications in this database (Keywords): Superoxide dismutase; Leishmania; ruthenium; metallodendrimer; cytochrome c reduction assay