Imidazole-containing phthalazine derivatives inhibit Fe-SOD performance in Leishmania species and are active in vitro against visceral and mucosal leishmaniasis - CORRIGENDUM

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作者：

M Sánchez-Moreno，F Gómez-Contreras，P Navarro，C Marín，I Ramírez-Macías，MJ Rosales，L Campayo，C Cano，AM Sanz，MJR Yunta

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摘要：

Thein vitroleishmanicidal activity of a series of imidazole-containing phthalazine derivatives1–4was tested onLeishmania infantum, Leishmania braziliensisandLeishmania donovaniparasites, and their cytotoxicity on J774·2 macrophage cells was also measured. All compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the threeLeishmaniaspecies, and the less bulky monoalkylamino substituted derivatives2and4were clearly more effective than their bisalkylamino substituted counterparts1and3. Both infection rate measures and ultrastructural alterations studies confirmed that2and4were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with2and4were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds2and4were potent inhibitors of iron superoxide dismutase enzyme (Fe-SOD) in the three species considered, whereas their impact on human CuZn-SOD was low. Molecular modelling suggests that2and4could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the antioxidant features of the enzyme.

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关键词：

Leishmania infantum Leishmania donovani Leishmania braziliensis iron superoxide dismutase imidazole phthalazine derivatives

DOI：

10.1017/S0031182015000219

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年份：

2015