scholarly journals Iron superoxide dismutase contributes to miltefosine resistance in Leishmania donovani

FEBS Journal ◽  
2019 ◽  
Vol 286 (17) ◽  
pp. 3488-3503 ◽  
Author(s):  
Jalaja Veronica ◽  
Sambamurthy Chandrasekaran ◽  
Alti Dayakar ◽  
Moodu Devender ◽  
Vijay Kumar Prajapati ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Leishmania Donovani ◽  
Iron Superoxide Dismutase

scholarly journals In vitro antileishmanial activity and iron superoxide dismutase inhibition of arylamine Mannich base derivatives

Parasitology ◽  
2017 ◽  
Vol 144 (13) ◽  
pp. 1783-1790 ◽  
Author(s):  
ALVARO MARTIN-MONTES ◽  
MERY SANTIVAÑEZ-VELIZ ◽  
ELSA MORENO-VIGURI ◽  
RUBÉN MARTÍN-ESCOLANO ◽  
CARMEN JIMÉNEZ-MONTES ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Leishmania Donovani ◽  
Mannich Base ◽  
Neglected Diseases ◽  
Leishmania Braziliensis ◽  
Reference Drug ◽  
Iron Superoxide Dismutase ◽  
Therapeutic Tools

SUMMARYLeishmaniasis is one of the world's most neglected diseases, and it has a worldwide prevalence of 12 million. There are no effective human vaccines for its prevention, and treatment is hampered by outdated drugs. Therefore, research aiming at the development of new therapeutic tools to fight leishmaniasis remains a crucial goal today. With this purpose in mind, we present 20 arylaminoketone derivatives with a very interesting in vitro and in vivo efficacy against Trypanosoma cruzi that have now been studied against promastigote and amastigote forms of Leishmania infantum, Leishmania donovani and Leishmania braziliensis strains. Six out of the 20 Mannich base-type derivatives showed Selectivity Index between 39 and 2337 times higher in the amastigote form than the reference drug glucantime. These six derivatives affected the parasite infectivity rates; the result was lower parasite infectivity rates than glucantime tested at an IC25 dose. In addition, these derivatives were substantially more active against the three Leishmania species tested than glucantime. The mechanism of action of these compounds has been studied, showing a greater alteration in glucose catabolism and leading to greater levels of iron superoxide dismutase inhibition. These molecules could be potential candidates for leishmaniasis chemotherapy.

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

Parasitology ◽  
2015 ◽  
Vol 142 (8) ◽  
pp. 1115-1129 ◽  
Author(s):  
M. SÁNCHEZ-MORENO ◽  
F. GÓMEZ-CONTRERAS ◽  
P. NAVARRO ◽  
C. MARÍN ◽  
I. RAMÍREZ-MACÍAS ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Leishmania Donovani ◽  
Cell Damage ◽  
Leishmania Species ◽  
The Other ◽  
Leishmania Braziliensis ◽  
Reference Drug ◽  
Iron Superoxide Dismutase ◽  
Mucosal Leishmaniasis

SUMMARYThe in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1–4 was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, 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 three Leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their bisalkylamino substituted counterparts 1 and 3. Both infection rate measures and ultrastructural alterations studies confirmed that 2 and 4 were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with 2 and 4 were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds 2 and 4 were 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 that 2 and 4 could 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.

Effect of Hubs in Amino Acid Network on Iron Superoxide Dismutase Stability

2015 ◽  
Vol 10 (2) ◽  
pp. 232-239
Author(s):  
Yanrui Ding ◽  
Xueqin Wang ◽  
Zhaolin Mou
Keyword(s):  
Superoxide Dismutase ◽  
Amino Acid ◽  
Iron Superoxide Dismutase
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