In Vitro and in Vivo Trypanosomicidal Activity of Pyrazole-Containing Macrocyclic and Macrobicyclic Polyamines: Their Action on Acute and Chronic Phases of Chagas Disease

Abstract

The in vitro and in vivo anti- Trypanosoma cruzi activity of the pyrazole-containing macrobicyclic polyamine 1 and N-methyl- and N-benzyl-substituted monocyclic polyamines 2 and 3 was studied. Activity against both the acute and chronic phases of Chagas disease was considered. The compounds were more active against the parasite and less toxic against Vero cells than the reference drug benznidazole, but 1 and 2 were especially effective, where cryptand 1 was the most active, particularly in the chronic phase. The activity results found for these compounds were complemented and discussed by considering their inhibitory effect on the iron superoxide dismutase enzyme of the parasite, the nature of the metabolites excreted after treatment, and the ultrastructural alterations produced. A complementary histopathological analysis confirmed that the compounds tested were significantly less toxic to mammals than the reference drug and that 1 and 2 exhibited lower levels of damage than 3.

In vitro leishmanicidal activity of pyrazole-containing polyamine macrocycles which inhibit the Fe-SOD enzyme of Leishmania infantum and Leishmania braziliensis species

“…1). Macrobicyclic polyamine 1 (Lamarque et al 2001), macrocyclic polyamines 2 and 3 (Arán et al 1999; Kumar et al 2001), with N-methyl- and N-benzyl-substituted pyrazole rings, and macrocyclic analogue 4 (Miranda et al 2004), with bulky octyl groups attached to the amine nitrogens on the side-chains had been previously tested by us against Trypanosoma cruzi (Sánchez-Moreno et al 2012 a ). In those assays it was found that compounds 1 – 3 were more active against the parasite and less toxic against Vero cells than the reference drug benznidazole (BZN), whereas the behaviour of 4 was similar to that of BZN or even worse.…”

<i>In Vitro</i> Activity of Squaramides and Acyclic Polyamine Derivatives against Trophozoites and Cysts of <i>Acanthamoeba castellanii</i>

“…The compounds tested were the squaramides and acyclic polyamines shown in Table 1. The solutions of the compounds were stored at −20˚C [27] [28]. These squaramides and acyclic polyamines are stable in this medium and can be stored without decomposition for long periods of time.…”

“…The antiparasitic activity of squaramides has been demonstrated, also, some showing antimalarial [26] and others antichagasic activity [27]. On the other hand, several macrocyclic scorpiand-like polyamines have proved effective against both the acute and chronic phases of Chagas disease [28].…”

Synthesis and in vitro leishmanicidal activity of novel [1,2,3]triazolo[1,5-a]pyridine salts

“…Use of intracellular forms is more laborious but allow us to obtain more accurate results, as they are transformed into amastigotes in vertebrate host cells. 29 Intracellular assays were performed by infecting macrophage cells with promastigotes, which transformed into amastigotes within 1 day aer infection. Table 1 shows the IC 50 values obtained aer 72 h of exposure to L. infantum, L. braziliensis and L. donovani species.…”

“…The cytotoxicity testing on macrophages was performed by ow cytometric analysis according to a method previously described. 29 The percentage of viable cells was calculated with respect to the control culture. The IC 50 was calculated using linear regression analysis from the K c values of the concentrations employed.…”