High antiparasitic activity of silver complexes of 5,7-dimethyl-1,2,4-triazolo[1,5 a]pyrimidine.

Two dinuclear silver complexes containing 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine (dmtp) were synthesized, [Ag2(dmtp)3]2[Ag2(dmtp)2](BF4)6(H2O)2 and [Ag2(dmtp)2(ClO4)2][Ag2(dmtp)2(H2O)2](ClO4)2. They have been spectroscopically and thermally characterized and their structures have been solved by single crystal X-ray diffraction. The compounds display fluorescence in the visible range (486 nm) when irradiated with UV light (265 nm). Both compounds, together with a previously reported analogue containing nitrate as counteranion, were assayed in vitro against three different species of Leishmania spp. and Trypanosoma cruzi, (parasites responsible for Leishmaniasis and Chagas disease) showing an extremely high antiparasitic activity, with IC50 values below the lower tested concentration (1 µM) for the three compounds and the four microorganisms, and hence a selectivity index better than those of the reference commercial drugs by more than one magnitude order, also improving the results of the free ligand and previously reported complexes with metals of the first transition series.

Índice C en médicos de dos centros hospitalarios chilenos según el test de competencia moral de Lind / Assessment of moral competence of physicians

Background: Moral competence (MC) in physicians is fundamental, given the increasing complexity of medicine. The "Moral Competence Test" (MCT © Lind) evaluates this feature and its indicator is the C Index (CI). Aim: To explore moral competence and its associated factors among physicians working in Chile. Material and Methods: The MCT was answered by 236 physicians from two medical centers who voluntarily participated in the study. Besides the test, participants completed an encrypted form giving information about gender, years in practice and post-graduate studies. Results: The average CI value of the participants was 20,9. Post-graduate studies had a significant positive influence on CI. There was a significant decrease in CI, between 16 and 20 years of professional exercise. Gender and the area of post-graduate studies did not have a significant influence. Conclusions: The studied physicians showed a wide range of CI which was positively affected by the postgraduate studies performed. The years of professional practice had a negative influence. Expanding training opportunities during professional practice could have a positive effect on CM as measured by CI.

Leishmanicidal and Trypanocidal Activity of Metal Complexes with 1,2,4-Triazolo[1,5-a]pyrimidines: Insights on their Therapeutic Potential against Leishmaniasis and Chagas Disease.

Since their first synthesis back in the early 20th century, 1,2,4-triazolo[1,5- a]pyrimidines have aroused increasing interest in very diverse areas ranging from chemotherapy to agriculture or even photography. Their similarity to purines confers a potential bioactivity and this feature has been wisely exploited for therapeutic use, including antifungal, antipyretic, analgesic, antiinflammatory, antitumoral and antiparasitic properties. In this review, we focus on the compounds that these nitrogen heterocycles form with metal ions and their antiparasitic activity and therapeutic potential against two neglected diseases of tropical prevalence, leishmaniasis and Chagas disease.

[Assessment of moral competence of physicians]. / Índice C en médicos de dos centros hospitalarios chilenos según el test de competencia moral de Lind.

BACKGROUND: Moral competence (MC) in physicians is fundamental, given the increasing complexity of medicine. The "Moral Competence Test" (MCT © Lind) evaluates this feature and its indicator is the C Index (CI). AIM: To explore moral competence and its associated factors among physicians working in Chile. MATERIAL AND METHODS: The MCT was answered by 236 physicians from two medical centers who voluntarily participated in the study. Besides the test, participants completed an encrypted form giving information about gender, years in practice and post-graduate studies. RESULTS: The average CI value of the participants was 20,9. Post-graduate studies had a significant positive influence on CI. There was a significant decrease in CI, between 16 and 20 years of professional exercise. Gender and the area of post-graduate studies did not have a significant influence. CONCLUSIONS: The studied physicians showed a wide range of CI which was positively affected by the postgraduate studies performed. The years of professional practice had a negative influence. Expanding training opportunities during professional practice could have a positive effect on CM as measured by CI.

Self-assembly synthesis, structure, topology, and magnetic properties of a mononuclear Fe(iii)-violurate derivative: a combined experimental and theoretical study.

A new iron(iii) complex [Fe(H2Vi)3]·py·4H2O (1) {H3Vi = violuric acid, py = pyridine} was self-assembled and characterized. In the crystal structure, adjacent [Fe(H2Vi)3] blocks are H-bonded into a complex 3D network, which was topologically classified as a pcu [alpha-Po primitive cubic] network. Importance of π-stacking interactions was also highlighted and analyzed computationally. Magnetic studies confirmed antiferromagnetic exchange coupling, while ZFCM/FCM experiments indicated an ordering temperature Tc = 50 K. Finally, magnetic hysteresis at 5 K possesses the coercive field of Bc = 69 mT.

Highly Stable Double-Stranded DNA Containing Sequential Silver(I)-Mediated 7-Deazaadenine/Thymine Watson-Crick Base Pairs.

The oligonucleotide d(TX)9 , which consists of an octadecamer sequence with alternating non-canonical 7-deazaadenine (X) and canonical thymine (T) as the nucleobases, was synthesized and shown to hybridize into double-stranded DNA through the formation of hydrogen-bonded Watson-Crick base pairs. dsDNA with metal-mediated base pairs was then obtained by selectively replacing W-C hydrogen bonds by coordination bonds to central silver(I) ions. The oligonucleotide I adopts a duplex structure in the absence of Ag(+) ions, and its stability is significantly enhanced in the presence of Ag(+) ions while its double-helix structure is retained. Temperature-dependent UV spectroscopy, circular dichroism spectroscopy, and ESI mass spectrometry were used to confirm the selective formation of the silver(I)-mediated base pairs. This strategy could become useful for preparing stable metallo-DNA-based nanostructures.

Triazolopyrimidine compounds containing first-row transition metals and their activity against the neglected infectious Chagas disease and leishmaniasis.

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.

Lanthanide complexes containing 5-methyl-1,2,4-triazolo[1,5-a] pyrimidin-7(4H)-one and their therapeutic potential to fight leishmaniasis and Chagas disease.

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.

H-bonds superstructures built by aquacomplexes and an azapurine derivative: a case of molecular recognition.

The crystal structures of six compounds involving the divalent cations of Mn, Zn and Cd, the anionic form of the heterocycle 4,6-dimethyl-1,2,3-triazolo[4,5-d]pyrimidin-5,7-dione (Hdmax) and bipyridyl based spacer ligands are reported. The most important feature of these structures is the presence, in all cases, of a topologically identical 1-D polymeric superstructure (tape), involving tetra- or hexaaqua complex cations and triazolopyrimidine anions, built through hydrogen bonds. Adding these results to others previously published, we may consider these tapes as robust supramolecular synthons where a defined/clear case of molecular recognition between these two moieties takes place.

In vitro anti-leishmania evaluation of nickel complexes with a triazolopyrimidine derivative against Leishmania infantum and Leishmania braziliensis.

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.

Insights on the binding ability of a new adenine analog: 7-amine-1,2,4-triazolo[1,5-a]pyrimidine. Synthesis and magnetic study of the first copper(II) complexes.

Conventional reactions of the new multidentate ligand 7-amine-1,2,4-triazolo[1,5-a]pyrimidine (7atp, 1) with copper(II) salts lead to four novel multidimensional coordination complexes [Cu(7atp)(mal)(H(2)O)(2)]·H(2)O (2), [Cu(2)(µ-7atp)(4)(H(2)O)(2)](ClO(4))(4)·3H(2)O (3), {[Cu(7atp)(2)(µ-ox)]·3H(2)O}(n) (4) and {[Cu(7atp)(2)(µ-suc)]·2H(2)O}(n) (5), where ox(2-), mal(2-) and suc(2-) mean oxalate, malonate and succinate, respectively. In these compounds, the 7atp ligand coordinates monodentately through its atom N3, except for compound 3, which displays N3-N4 coordination mode, giving rise to all to structures with diverse topologies and dimensionality. Compound 2 is a mononuclear entity, 3 consists of dinuclear species, 4 is a zig-zag chain with oxalate as a bridging ligand and 5 is a succinate-bridged mono-dimensional system. All polynuclear metal complexes show antiferromagnetic interactions of with J values ranging from -0.12 to -49.5 cm(-1). The ligand donor capabilities have been estimated by topological analyses of the electron density (QTAIM) and electron localization function (ELF), obtained by DFT calculations. The compounds are the first structurally characterized copper(II) complexes containing the 7atp ligand.

Dinuclear silver(I) complexes for the design of metal-ligand networks based on triazolopyrimidines.

Silver(I) coordination complexes with the versatile and biomimetic ligands 1,2,4-triazolo[1,5-a]pyrimidine (tp), 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) and 7-amine-1,2,4-triazolo[1,5-a]pyrimidine (7atp) all feature dinuclear [Ag(2)(µ-tp)(2)](2+) building units (where tp is a triazolopyrimidine derivative), which are the preferred motif, independently of the counter-anion used. According to AIM (atoms in molecules) and ELF (electron localization function) analyses, this fact is due to the great stability of these dinuclear species. The complexes structures range from the dinuclear entities [Ag(2)(µ-tp)(2)(CH(3)CN)(4)](BF(4))(2) (1), [Ag(2)(µ-tp)(2)(CH(3)CN)(4)](ClO(4))(2) (2), [Ag(2)(µ-7atp)(2)](ClO(4))(2) (3) and [Ag(2)(µ-dmtp)(2)(CH(3)CN)](PF(6))(ClO(4)) (4) over the 1D polymer chain [Ag(2)(µ-CF(3)SO(3))(2)(µ-dmtp)(2)](n) (5) to the 3D net {[Ag(2)(µ(3)-tp)(2)](PF(6))(2)·âˆ¼6H(2)O}(n) (6) with NbO topology.

Structural and magnetic properties of three novel complexes with the versatile ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one.

Conventional reactions of the versatile multidentate ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) with metallic(II) 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). In each compound, the triazolopyrimidine ligand shows a different and unusual coordination mode, giving rise to structures with diverse topologies and dimensionality. Compound 1 is a monomeric complex, in which HmtpO shows both N3-monodentate and N1,O71-bidentate modes. 2 is a bidimensional framework with the ligand showing a N3,O71 bidentate-bridging mode. The structure of 3 consists of 1D chains, in which HmtpO displays a N1,N3,O71-tridentate-bridging mode. It should be noted that these coordination modes of the HmtpO ligand are unique in the case of compounds 2 and 3. On the other hand, the magnetic properties of the polynuclear complexes 2 and 3 have been studied showing weak ferromagnetic and antiferromagnetic behaviour, respectively.

Bis(cyanato-κN)bis-(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-κN)zinc.

In the title complex, [Zn(NCO)(2)(C(7)H(8)N(4))(2)], the Zn(II) ion exhibits a distorted tetra-hedral coordination geometry. The coordination environment is formed by two 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) ligands, coordinated through the N atom in position 3, and two cyanate anions inter-acting by their N atoms. Supra-molecular dimers are generated by stacking inter-actions between the pyrimidine rings of two ligands related by an inversion center [centroid-centroid distance = 3.5444 (18) Å].

In vitro and in vivo antiparasital activity against Trypanosoma cruzi of three novel 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one-based complexes.

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.

Bis(7-amino-1,2,4-triazolo[1,5-a]pyrimidin-4-ium) bis-(oxalato-κO,O)cuprate(II) dihydrate.

The structure of the title ionic compound, (C(5)H(6)N(5))(2)[Cu(C(2)O(4))(2)]·2H(2)O, consists of a centrosymmetric copper(II) oxalate dianion, two monoprotonated mol-ecules of the adenine analog 7-amino-1,2,4-triazolo[1,5-a]pyrimidine (7atp) and two water mol-ecules of crystallization. The Cu(II) ion, located on an inversion center, exhibits a sligthly distorted square-planar coordination geometry, in which two oxalate anions bind in a bidentate fashion. The triazolopyrimidine ligand is protonated at the N atom in position 4, instead of its most basic N atom in position 3. This fact may be explained by the network stability, which is provided through the formation of a two-dimensional wave-like network parallel to (50[Formula: see text]) by N-H⋯O, O-H⋯N and O-H⋯O hydrogen bonds. These nets are further connected via C-H⋯O inter-actions.

In vitro and in vivo trypanocidal evaluation of nickel complexes with an azapurine derivative against Trypanosoma cruzi.

Seven ternary nickel(II) complexes (three previously described and four firstly described here) with an azapurine derivative (the anionic form of 4,6-dimethyl-1,2,3-triazolo[4,5-d]pyrimidin-5,7-dione) have been synthesized and spectroscopically characterized, and the crystal structures of three of them have been solved by X-ray diffraction. Studies in vitro and in vivo on the antiproliferative activity of these complexes against Trypanosoma cruzi (epimastigote, amastigote, and trypomastigote forms) have been carried out, displaying in some cases significantly higher antitrypanosomatid activity and lower toxicity than the reference drug for Chagas' disease, benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide). Ultrastructural analysis and metabolism excretion studies were also executed in order to propose a possible mechanism of action for the assayed drugs.

4,7-Phenanthrolinium perchlorate-5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one-water (1/1/2).

The asymmetric unit of the title compound, C(12)H(9)N(2) (+)·ClO(4) (-)·C(6)H(6)N(4)O·2H(2)O, contains a monoprotonated 4,7-phenanthrolinium (47phen) cation, a perchlorate anion balancing its charge, a neutral mol-ecule of 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) and two inter-stitial water mol-ecules. In the crystal structure, the acidic H atoms of 47phenH(+) and HmtpO form strong hydrogen bonds with the water mol-ecules, which in turn act as hydrogen-bond donors, forming links between them and towards the carbonyl O atom of HmtpO, the non-protonated N atom of 47phen(+) and one of the O atoms of the anion.

Versatile binding behaviour of 4,6-dimethyl-1,2,3-triazolo[4,5-d]-pyrimidin-5,7-dionato in the presence of bipyrimidine. Supramolecular H-bond architectures.

Complexes with the ligand 4,6-dimethyl-1,2,3-triazolo-[4,5-d]-pyrimidin-5,7-dionato (dmax(-)) and the auxiliary chelating-bridging ligand bipyrimidine (bpym) have been synthesized and structurally characterized for the divalent cations of Zn, Cd and Cu. For Zn and Cd, dinuclear complexes with the formulae [Zn(2)(dmax)(4)(H(2)O)(2)(bpym)].2H(2)O and [Cd(2)(dmax)(4)(H(2)O)(4)(bpym)].6H(2)O have been isolated whereas for Cu, the one-dimensional polymer {[Cu(2)(dmax)(4)(bpym)].5H(2)O}(n) has been obtained. Bpym acts as a chelating-bridging ligand in the three compounds, joining couples of metal ions. Two crystallographically and chemically different dmax(-) ligands are present in each of these complexes, one monodentately linked via the triazole N atom furthest from the pyrimidine ring (N2) and the other either monodentately linked via the triazole N atom closer to a carbonyl group (N1, Zn and Cd compounds) or in bridging N1-N2 mode (Cu compound), in the latter case generating an one-dimensional polymer with alternating bpym and (dmax)(2) bridges. The magnetic interaction across the bpym bridge gives rise to a strong antiferromagnetic interaction (2J = -201 cm(-1)), whereas that across the (dmax)(2) bridge is negligible and cannot be reliably determined (obscured by the strong one). The hydrogen bonds between water molecules and the triazolopyrimidine derivative build the 3-D structure of the compounds.

Copper (II) complexes of [1,2,4]triazolo [1,5-a]pyrimidine derivatives as potential anti-parasitic agents.

Anti-proliferative effects are described for newly synthesised copper (II) complexes of two triazolo-pyrimidine derivatives (1,2,4-triazolo-[1,5-a]pyrimidine, tp, and 5,7-dimethyl 1,2,4-triazolo-[1,5-a]pyrimidine, dmtp) against to Trypanosoma cruzi and Leishmania (Viannia) peruviana. Of the compounds assayed, those that presented the ligand tp and auxiliary ligand 1,10-phenanthroline (C24b, C49) were most highly active against to T. cruzi with IC(50) within the range of the reference drug benznidazole. These compounds, together with C35 were the most effective against L. (V.) peruviana with an IC(50) greater than that presented by reference drugs (Pentostam and Glucantim). These compounds were not toxic to the host cell. IC(25) diminished the infection capacity and severely reduced the multiplication of intracellular forms of T. cruzi, and L. (V.) peruviana. In the case of T. Cruzi, the transformation to trypomastigote was seriously depressed. Copper (II) complexes C24b, C49 and C35, acted on the energy metabolism of the parasites at the level of the NAD(+)/NADH balance and at the level of the organelle membranes, causing degradation and cell death.