1,4-Bis(alkylamino)benzo[g]phthalazines able to form dinuclear complexes of Cu(II) which as free ligands behave as SOD inhibitors and show efficient in vitro activity against Trypanosoma cruzi

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

“…1, formulae I–VII ). All these compounds exhibit remarkable affinity towards transition metals (Lamarque et al 2001; Rodríguez-Ciria et al 2007; Blasco et al 2010); and are, simultaneously, powerful inhibitors of parasitic Fe-SOD, although poorer inhibitors of human CuZn-SOD. This is the case with pyrazole-containing macrocyclic and macrobicyclic polyamines I and II (Sánchez-Moreno et al 2012 a ) and with pyridine-containing scorpiand-like azamacrocycles III (Olmo et al 2013), in which their inhibitory ability against T. cruzi Fe-SOD runs in parallel with in vitro trypanocidal properties and in vivo activity against both acute and chronic phases of Chagas disease.…”

In vitro Leishmanicidal and Trypanosomicidal Properties of Imidazole‐Containing Azine and Benzoazine Derivatives

“…In all cases, their inhibiting features were found to be related to the high complexing potentiality of the polyaminic structures assayed, since the environment of the active site could be modified by complexation. [20][21][22][23][24]28] Therefore, the effects of the compounds showing better selectivity index against each of the four parasites under study on the corresponding parasite Fe-SOD, were assayed at concentrations ranging from 1 μM to 100 μM. In each case, epimastigote (Trypanosoma) or promastigote (Leishmania) forms of the parasite, which excreted Fe-SOD when cultured in a medium lacking inactive fetal calf serum (FCS), were used.…”

“…In connection with this matter, our group has been working in the last years in the synthesis and antiparasitic properties of different series of phthalazine derivatives functionalized with imidazole or pyrazole rings at the end of sidechains attached to the pyridazine moiety. [ 20 , 21 , 22 , 23 , 24 ] According to the antiparasitic activity reported previously for many azole compounds, some of these series containing the imidazole moiety have shown interesting activity data against T. cruzi and/or different Leishmania species, and those properties seem to be related to the simultaneous presence of both the pyridazine and the imidazole heterocyclic systems, clearly showing structure dependence for both trypanocidal and leishmanicidal features.…”

Hydrogen-bonded sheets in benzylmethylammonium hydrogen maleate

“…The compound was obtained during an attempt to prepare -(benzylmethylamino)succinic anhydride, (II) (see scheme), for use as an intermediate in the synthesis of new fused heterocyclic systems. Synthetic targets potentially accessible from intermediates of type (II) include amino-substituted phthalazines, which show activity as inhibitors of speci®c enzymes, such as human liver aldehyde oxidase (Beedham et al, 1995) and superoxide dismutase (Rodriguez-Ciria et al, 2007), as well as activity against seizures induced by electroshock (Sivakumar et al, 2002), and fused 1,3-diazepines, which show activity against the hepatitis-B and hepatitis-C viruses (Zhang et al, 2005). The intended synthesis of (II) involved a Michael-type reaction between benzylmethylamine and maleic anhydride, but evidently hydrolysis occurred during this procedure so that compound (I) was obtained instead, albeit in low yield.…”