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Purpose: The aim of the present investigation is to study the relationship of ventricular global longitudinal strain (GLS) and ultrasound lung comets (ULC) formation to establish a link between extravascular pulmonary water formation and cardiac contractile dysfunction., Methods: This is a prospective observational study including 14 active military divers. The subjects performed two sea dives of 120 min each with a semi-closed SCUBA circuit at 10 m depth. Divers were examined at baseline, 15 min (D1) and 60 min (D2) after diving. The evaluation included pulmonary and cardiac echography (including speckle tracking techniques). Blood samples were drawn at baseline and after diving, assessing hs-TnT and Endothelin-1., Results: ULC were detected in 9 (64.2%) and 8 (57.1%) of the subjects after D1 and D2 respectively. No differences were found in right and left ventricular GLS after both immersions (RV: Baseline:  - 17.9 4.9 vs. D1:  - 17.2 6.5 and D2:  - 16.7 5.8 s -1 ; p = 0.757 and p = 0.529; LV: Baseline:  - 17.0 2.3 vs. D1:  - 17.4 2.1 and D2:  - 16.9 2.2 s -1 ; p = 0.546 and p = 0.783). However, a decrease in atrial longitudinal strain parameters have been detected after diving (RA: Baseline: 35.5 9.2 vs. D1: 30.3 12.8 and D2: 30.7 13.0 s -1 ; p = 0.088 and p = 0.063; LA: Baseline: 39.0 10.0 vs. D1: 31.6 6.1 and D2: 32.4 10.6 s -1 ; p = 0.019 and p = 0.054)., Conclusion: In the present study, no ventricular contractile dysfunction was observed. However, increase pulmonary vasoconstriction markers were present after diving., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Atherosclerosis is a chronic, progressive, inflammatory disease in the vasculature and is common in both coronary and peripheral arteries. Human beings harbor a complex and dynamic population of microorganisms defined as the microbiota. Importantly, alterations in the bacterial composition (dysbiosis) and the metabolic compounds produced by these bacteria have been associated with the pathogenesis of many inflammatory diseases and infections. There is also a close relationship between intestinal microbiota and cardiovascular diseases. The aim of this review was to analyze how changes in the gut microbiota and their metabolites might affect coronary artery diseases. The most representative groups of bacteria that make up the intestinal microbiota are altered in coronary artery disease patients, resulting in a decrease in Bacteroidetes and an increase in Firmicutes . In relation to metabolites, trimethylamine-N-oxide plays an important role in atherosclerosis and may act as a cardiovascular risk predictor. In addition, the use of probiotics, prebiotics, diet modulation, and fecal transplantation, which may represent alternative treatments for these diseases, is thoroughly discussed. Finally, the role of lipid-lowering treatments is also analyzed as they may affect and alter the gut microbiota and, conversely, gut microbiota diversity could be associated with resistance or sensitivity to these treatments.

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.

The efficacy and safety of vitamin K antagonists (VKAs) as oral anticoagulants (OACs) depend on the quality of anticoagulation control, as reflected by the mean time in therapeutic range (TTR). Several factors may be involved in poor TTR such as comorbidities, high inter-individual variability, interacting drugs, and non-adherence. Recent studies suggest that gut microbiota (GM) plays an important role in the pathogenesis of cardiovascular diseases, but the effect of the GM on anticoagulation control with VKAs is unknown. In the present review article, we propose different mechanisms by which the GM could have an impact on the quality of anticoagulation control in patients taking VKA therapy. We suggest that the potential effects of GM may be mediated first, by an indirect effect of metabolites produced by GM in the availability of VKAs drugs; second, by an effect of vitamin K-producing bacteria; and finally, by the structural modification of the molecules of VKAs. Future research will help confirm these hypotheses and may suggest profiles of bacterial signatures or microbial metabolites, to be used as biomarkers to predict the quality of anticoagulation. This could lead to the design of intervention strategies modulating gut microbiota, for example, by using probiotics.

Introduction: Oral anticoagulants (OAC) reduce stroke/systemic embolism and mortality risks in atrial fibrillation (AF). However, there is an inherent bleeding risk with OAC, where intracranial hemorrhage (ICH) is the most feared, disabling, and lethal complication of this therapy. Therefore, the optimal management of OAC-associated ICH is not well defined despite multiple suggested strategies., Areas Covered: In this review, the authors describe the severity and risk factors for OAC-associated ICH and the associated implications for using DOACs in AF patients. We also provide an overview of the management of OAC-associated ICH and treatment reversal strategies, including specific and nonspecific reversal agents as well as a comprehensive summary of the evidence about the resumption of DOAC and the optimal timing., Expert Opinion: In the setting of an ICH, supportive care/measures are needed, and reversal of anticoagulation with specific agents (including administration of vitamin K, prothrombin complex concentrates, idarucizumab and andexanet alfa) should be considered. Most patients will likely benefit from restarting anticoagulation after an ICH and permanently withdrawn of OAC is associated with worse clinical outcomes. Although the timing of OAC resumption is still under debate, reintroduction after 4-8 weeks of the bleeding event may be possible, after a multidisciplinary approach to decision-making.

In cardiovascular disease (CVD), biomarkers (i.e., "biological markers") could have multiple roles in understanding the complexity of cardiovascular (CV) pathophysiology and to offer an integrated approach to management. Biomarkers could help in daily practice as a diagnostic tool, to monitor therapy response, to assess prognosis and as early marker of CV damage, or to stratify risk. In recent years, the role of biomarkers in CVD is even more relevant and some have recently been included in clinical management guideline recommendations. The aim of this review is to discuss the recommendations in clinical guidelines of various biomarkers and to review their usefulness in daily clinical practice. Ultimately, a balance is needed between simplicity and practicality for clinical decision-making. Most biomarkers (whether blood, urine, or imaging-based) will improve on clinical risk stratification, but awaiting biomarker results may lead to delays in the initiation of therapy, for example, anticoagulation for stroke prevention in atrial fibrillation. Many biomarkers are nonspecific, being predictive of many CV and non-CV outcomes, so would be better as "rule-out" rather than "rule-in" assessments. Derivation of some biomarkers have also been made in highly selected clinical trial cohorts, where measurement is made at baseline but outcomes determined many years later; given the dynamic nature of risk in the "real world" where patients get older and develop incident risk factors, this may give a false impression of the risk profile. Finally, some laboratory biomarkers have a diurnal variation and inter-/intravariability (and lower limits of detection) in assays, which may be expensive, are added considerations., Competing Interests: F.M. has received fees for educational purposes for Boehringer-Ingelheim and Daiichi Sankyo and as advisory board of Boehringer-Ingelheim, Bayer, Pfizer, Daiichi Sankyo, and Atrial Fibrillation Network (AFNET). V.R. has received fees for educational purposes for Boehringer-Ingelheim and Pfizer, and investigator fees for Boehringer-Ingelheim. G.Y.L. has served as a consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo and as a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees were directly received personally. The authors have no other funding, financial relations, or conflicts of interest to disclose related to this work., (Georg Thieme Verlag KG Stuttgart · New York.)

The spectrum and efficacy of available antileishmanial drugs is limited. In the present work we evaluated in vitro the antiproliferative activity of 11 compounds based on tetradentate polyamines compounds against three Leishmania species ( L. braziliensis , L. donovani and L. infantum ) and the possible mechanism of action. We identified six compounds ( 3 , 5 , 6 , 7 , 8 and 10 ) effective against all three Leishmania spp both on extracellular and intracellular forms. These six most active leishmanicidal compounds also prevent the infection of host cells. Nevertheless, only compound 7 is targeted against the Leishmania SOD. Meanwhile, on the glucose metabolism the tested compounds have a species-specific effect on Leishmania spp.: L. braziliensis was affected mainly by 10 and 8 , L. donovani by 7 , and L. infantum by 5 and 3 . Finally, the cellular ultrastructure was mainly damaged by 11 in the three Leishmania spp. studied. These identified antileishmania candidates constitute a good alternative treatment and will be further studied.

The synthesis and antiprotozoal activity of some simple dialkyl pyrazole-3,5-dicarboxylates (compounds 2-6) and their sodium salts (pyrazolates) (compounds 7-9) against Trypanosoma cruzi, Leishmania infantum and Leishmania braziliensis are reported. In most cases the studied compounds showed, especially against the clinically significant amastigote forms, in vitro activities higher than those of the reference drugs (benznidazole for T. cruzi and glucantime for Leishmania spp.); furthermore, the low non-specific cytotoxicities against Vero cells and macrophages shown by these compounds led to good selectivity indexes, which are 8-72 times higher for T. cruzi amastigotes and 15-113 times higher for Leishmania spp. amastigotes than those of the respective reference drugs. The high efficiency of diethyl ester 3 and its sodium salt 8 against the mentioned protozoa was confirmed by further in vitro assays on infection rates and by an additional in vivo study in a murine model of acute and chronic Chagas disease. The inhibitory capacity of compounds 3 and 8 on the essential iron superoxide dismutase of the aforementioned parasites may be related to the observed anti-trypanosomatid activity. The low acute toxicity of compounds 3 and 8 in mice is also reported in this article.

The antiprotozoal activity of some indazole-derived amines (2, 3, 5-8) as well as that of some simple structurally related 3-alkoxy-1-alkyl-5-nitroindazoles (1, 4) against promastigote and amastigote forms of Leishmania infantum and Leishmania braziliensis is reported. In some cases, these compounds showed in vitro activities against the different morphological forms of Leishmania similar to or higher than those of the reference drug glucantime; this fact, along with low unspecific cytotoxicities against macrophages shown by some of them, led to good selectivity indexes (SI). The high efficiency of some 5-nitroindazoles against the mentioned protozoa was confirmed by further in vitro studies on infection rates. Complementary analyses by (1)H NMR of the changes on the metabolites excreted by parasites after treatment with the more active indazole derivatives in many cases showed the decreased excretion of succinate and increased levels of acetate, lactate and alanine, as well as, in some cases, the appearance of glycine and pyruvate as new metabolites. Damage caused by indazoles at the glycosomal or mitochondrial level are consistent with these metabolic changes as well as with the huge ultrastructural alterations observed by transmission electron microscopy (TEM), especially affecting the mitochondria and other cytoplasmic organelles., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Leishmaniasis and Chagas disease remain a significant global problem. Current treatments have serious disadvantage due to cost, toxicity, long therapy duration and resistance. In the last years increasing interest has arisen in drug development to fight both diseases. Recently, metal-based drugs have revealed as promising drugs in a variety of therapeutic areas. Herein we describe six newly synthesized transition metal complexes with a bioactive molecule 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp). All of them have been characterized by X-ray, spectroscopic and thermal methods. In vitro and in vivo studies (murine model) on the antiproliferative activity of these complexes against Leishmania spp. (Leishmania infantum, Leishmania braziliensis) and Trypanosoma cruzi have been carried out. Our results reveal a strong potential of three of the assayed compounds as antiparasitic agents against the above-mentioned infectious diseases., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

In the last years, numerous and significant advances in lanthanide coordination chemistry have been achieved. The unique chemical nature of these metal ions which is conferred by their f-electrons has led to a wide range of coordination compounds with interesting structural, physical and also biological properties. Consequently, lanthanide complexes have found applications mainly in catalysis, gas adsorption, photochemistry and as diagnostic tools. However, research on their therapeutic potential and the understanding of their mechanism of action is still taking its first steps, and there is a distinct lack of research in the parasitology field. In the present work, we describe the synthesis and physical properties of seven new lanthanide complexes with the anionic form of the bioactive ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO), namely [Ln(mtpO)3(H2O)6]·9H2O (Ln=La(III), Nd(III), Eu(III), Gd(III), Tb(III), Dy(III) and Er(III)). In addition, results on the in vitro antiproliferative activity against Leishmania spp. and Trypanosoma cruzi are described. The high activity of the new compounds against parasite proliferation and their low cytotoxicity against reference host cell lines show a great potential of this type of compounds to become a new generation of highly effective and non-toxic antiparasitic agents to fight the so considered neglected diseases leishmaniasis and Chagas disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The synthesis and antiprotozoal activity of some 3-alkoxy-1-alkyl- (1, 4) and 3-alkoxy-1-(ω-aminoalkyl)-5-nitroindazoles (2, 3, 5-8) against different morphological forms of Trypanosoma cruzi are reported. These compounds were prepared using simple alkylation reactions and, usually, taking advantage of the reactivity of some indazole-derived betaines previously studied by us. Most indazole derivatives showed in vitro activities similar or higher than those of the reference drug benznidazole; this fact, along with low unspecific cytotoxicities against Vero cells shown by some of them, led to very good selectivity indexes (SI). The high efficiency of 5-nitroindazoles 1 and 2 against T. cruzi was confirmed by further in vitro studies on infection rates and by an additional in vivo study in a murine model of acute and chronic Chagas disease. Complementary analyses of the changes in the metabolites excreted by the parasite and on the ultrastructural alterations induced after treatment with indazole derivatives 1 and 2 were also conducted., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Access to basic drugs is a major issue in developing countries. Chagas disease caused by Trypanosoma cruzi is a paradigmatic example of a chronic disease without an effective treatment. Current treatments based on benznidazole and nifurtimox are expensive, ineffective, and toxic. N,N'-Squaramides are amide-type compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites. When combined with amine and carboxylic groups, squaramide compounds have increased solubility and therefore make suitable therapeutic agents. In this work, we introduce a group of Lipinski's rule of five compliant squaramides as candidates for treating Chagas disease. The in vivo studies confirmed the positive expectations arising from the preliminary in vitro studies, revealing compound 17 to be the most effective for both acute and chronic phases. The activity, stability, low cost of starting materials, and straightforward synthesis make amino squaramides appropriate molecules for the development of an affordable anti-Chagasic agent.

The activity of a family scorpiand-like azamacrocycles against Leishmania infantum and Leishmania braziliensis was studied using promastigotes, axenic and intracellular amastigotes forms. All the compounds are more active and less toxic than meglumine antimoniate (Glucantime). Moreover, the data on infection rates and amastigotes showed that compounds P2Py, PN and P3Py are the most active against both species of Leishmania. On the other hand, studies on the inhibitory effect of these compounds on SOD enzymes showed that while the inhibition of the Fe-SOD enzyme of the promastigote forms of the parasites is remarkable, the inhibition of human CuZn-SOD and Mn-SOD from Escherichia coli is negligible. The ultrastructural alterations observed in treated promastigote forms confirmed that the compounds having the highest activity were those causing the largest cell damage. The modifications observed by (1)H NMR, and the amounts of catabolites excreted by the parasites after treatment with the compounds, suggested that the catabolic mechanism could depend on the structure of the side chains linked to the aza-scorpiand macrocycles., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The in vitro leishmanicidal (Leishmania infantum and Leishmania braziliensis) and trypanocidal (Trypanosoma cruzi) activities of different compounds were evaluated. These compounds, of vegetal origin but synthesised in our laboratory, included five taiwaniaquinoid derivatives (S-567; S-569; S-589; S-602 and A-246) and one abietane quinone (P-1). The in vitro activity of the compounds on extracellular and intracellular forms of the two Leishmania species and T. cruzi was assayed. Infectivity and cytotoxicity tests for the Leishmania species were conducted on J774.2 macrophage cells using Glucantime as the reference drug. From all the compounds assayed, the derivatives P-1>S-567 were more active and less toxic than Glucantime. Infection rates and amastigote means indicated that these two compounds were the most active in both Leishmania species. In the case of T. cruzi, the best derivatives were P-1 and S-567, at the same levels as for the Leishmania species. These compounds exhibited the most potent anti-proliferative activity against the extracellular vector form (the epimastigote), the extracellular host form (the trypomastigote), and the intracellular host form (the amastigote), with lower toxicity than that of the reference drug Benznidazole. Metabolite excretion studies showed that alterations mainly at the level of the mitochondria may explain observed metabolic changes in succinate and acetate production, perhaps due to the disturbance of enzymes involved in sugar metabolism within the mitochondrion. The in vivo studies for T. cruzi provided results consistent with those found in vitro. No signs of toxicity were detected in mice treated with the compounds tested, and the parasitic charge was slightly lower than in the control. The effects of these two compounds were also demonstrated with the change in the anti-T. cruzi antibody levels during the chronic stage., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Four terpenoid derivatives were examined for their activity against Trypanosoma cruzi. Our results show that two compounds were very active in vitro against both extra- and intracellular forms. These compounds, non-toxic for the host cells, are more effective than the reference drug benznidazole. The capacity to infect cells was negatively affected and the number of amastigotes and trypomastigotes was reduced. A wide range of ultrastructural alterations was found in the epimastigote forms treated with these compounds. Some metabolic changes occurred presumably at the level of succinate and acetate production, perhaps caused by the disturbance of the enzymes involved in sugar metabolism inside the mitochondria. In vivo results were consistent with those observed in vitro. The parasitic load was significantly lower than in the control assay with benznidazole. The effects of these products showed the reduction of the anti-T. cruzi antibodies level during the chronic stage.

Studies on the anti-proliferative activity in vitro of seven ternary nickel (II) complexes with a triazolopyrimidine derivative and different aliphatic or aromatic amines as auxiliary ligands against promastigote and amastigote forms of Leishmania infantum and Leishmania braziliensis have been carried out. These compounds are not toxic for the host cells and two of them are effective at lower concentrations than the reference drug used in the present study (Glucantime). In general, the in vitro growth rate of Leishmania spp. was reduced, its capacity to infect cells was negatively affected and the multiplication of the amastigotes decreased. Ultrastructural analysis and metabolism excretion studies were executed in order to propose a possible mechanism for the action of the assayed compounds. Our results show that the potential mechanism is at the level of organelles membranes, either by direct action on the microtubules or by their disorganization, leading to vacuolization, degradation and ultimately cell death., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The activity of five (1-5) abietane phenol derivatives against Leishmania infantum and Leishmania braziliensis was studied using promastigotes and axenic and intracellular amastigotes. Infectivity and cytotoxicity tests were performed with J774.2 macrophage cells using Glucantime as a reference drug. The mechanisms of action were analysed by performing metabolite excretion and transmission electron microscopy ultrastructural studies. Compounds 1-5 were more active and less toxic than Glucantime. The infection rates and mean number of parasites per cell observed in amastigote experiments showed that derivatives 2, 4 and 5 were the most effective against both L. infantum and L. braziliensis. The ultrastructural changes observed in the treated promastigote forms confirmed that the greatest cell damage was caused by the most active compound (4). Only compound 5 caused changes in the nature and amounts of catabolites excreted by the parasites, as measured by ¹H nuclear magnetic resonance spectroscopy. All of the assayed compounds were active against the two Leishmania species in vitro and were less toxic in mammalian cells than the reference drug.

Objectives: To evaluate the in vitro leishmanicidal activity of nine flavonoid derivatives from Delphinium staphisagria against L. infantum and L. braziliensis., Design and Methods: The in vitro activity of compounds 1-9 was assayed on extracellular promastigote and axenic amastigote forms and on intracellular amastigote forms of the parasites. Infectivity and cytotoxicity tests were carried on J774.2 macrophage cells using Glucantime as the reference drug. The mechanisms of action were analysed performing metabolite excretion and transmission electronic microscope ultrastructural alteration studies., Results: Nine flavonoids showed leishmanicidal activity against promastigote as well as amastigote forms of Leishmania infantum and L. braziliensis. These compounds were nontoxic to mammalian cells and were effective at similar concentrations up to or lower than that of the reference drug (Glucantime). The results showed that 2(″)-acetylpetiolaroside (compound 8) was clearly the most active., Conclusion: This study has demonstrated that flavonoid derivatives are active against L. infantum and L. braziliensis.

Conventional reactions of the versatile multidentate ligand 5-methyl-1,2,4-triazolo[1,5-a] pyrimidin-7(4H)-one (HmtpO) with metallic(II) perchlorate salts lead to three novel multidimensional complexes [Cu(HmtpO)(2)(H(2)O)(3)](ClO(4))(2)·H(2)O (1), {[Cu(HmtpO)(2)(H(2)O)(2)](ClO(4))(2) ·2HmtpO}(n) (2) and {[Co(HmtpO)(H(2)O)(3)](ClO(4))(2)·2H(2)O}(n) (3). We have tested the antiparasital activity in vitro and in vivo of the three new complexes against Trypanosoma cruzi showing very promising results and overcoming clearly the reference drug commonly used for the Chagas disease treatment, benznidazole., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The in vitro and in vivo trypanocidal activities of nine flavonoids (1-9) isolated from the aerial parts of Delphinium staphisagria have been studied in both the acute and chronic phases of Chagas disease. The antiproliferative activity of these substances against Trypanosoma cruzi (epimastigote, amastigote, and trypomastigote forms) in some cases exhibited more potent antitrypanosomatid activity and lower toxicity than the reference drug, benznidazole. Studies in vitro using ultrastructural analysis together with metabolism-excretion studies were also performed in order to identify the possible action mechanism of the compounds tested. Alterations mainly at the level of the mitochondria may explain metabolic changes in succinate and acetate production, perhaps due to the disturbance of the enzymes involved in sugar metabolism within the mitochondrion. In vivo studies provided results consistent with those observed in vitro. No signs of toxicity were detected in mice treated with the flavonoids tested, and the parasitic charge was significantly lower than in the control assay with benznidazole. The effects of these compounds were also demonstrated with the change in the anti-T. cruzi antibody levels during the chronic stage.

Objectives: We report on new 1,2,4-triazolo[1,5-a]pyrimidine complexes that have been developed and examined for both antiproliferative in vitro activity against Leishmania infantum and Leishmania braziliensis, and report their possible mechanism of action on L. infantum and L. braziliensis., Results: Antileishmanial effects are described for newly synthesized Cu(II) and Co(II) complexes containing 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) as a ligand. These complexes display a wide structural diversity: (i) mononuclear unit, [Cu(HmtpO)2(H2O)3](ClO4)2·H2O (1); (ii) two-dimensional framework, {[Cu(HmtpO)2(H2O)2](ClO4)(2)·2HmtpO}n (2); and (iii) chains, {[Co(HmtpO)(H2O)3](ClO4)(2)·2H2O}n (3). Compounds 1 and 2 appeared to be the most active against L. infantum (IC50 20.0 and 24.4 μM, respectively), and compounds 1 and 3 the most active against L. braziliensis (IC50 22.1 and 23.5 μM, respectively), with IC50s similar to those of the reference drug, glucantime (18.0 μM for L. infantum and 25.6 μM for L. braziliensis). These compounds were not toxic towards J774.2 macrophages. IC25 decreased infection capacity and severely reduced the multiplication of intracellular amastigotes, following the trend 1>3>2 for L. infantum and 3>1>2 for L. braziliensis. These complexes had an effect on the energy metabolism of the parasites at the level of the NAD+/NADH balance and the organelle membranes, causing their degradation and cell death., Conclusions: Cellular proliferation, metabolic and ultrastructural studies showed that the compounds 2>1>3 were highly active against L. infantum and L. braziliensis.