Análisis de eventos adversos en los servicios de cirugía general y aparato digestivo. Estudio multicéntrico / Analysis of adverse events in general surgery: A multicenter study

Introducción: El conocimiento de los eventos adversos (EA) en los hospitales de agudos es un aspecto de especial relevancia en la seguridad del paciente. Su incidencia oscila entre un 3-17% y la cirugía se relaciona con la aparición de entre un 46-65% de todos los EA. Material y métodos: Se realiza un estudio observacional, descriptivo, retrospectivo y multicéntrico, con la participación de 31 hospitales de agudos españoles, para la determinación y análisis de los EA en los servicios de cirugía general. Resultados: La prevalencia de EA fue del 31,53%. Los tipos de EA más frecuentes fueron de tipo infeccioso (35%). Los pacientes con mayores grados de ASA, mayor complejidad y un tipo de ingreso urgente son factores asociados a la presencia de EA. A la mayoría de los pacientes se les atribuyó una categoría de daño F (daño temporal al paciente que requiera iniciar o prolongar la hospitalización) (58,42%). El 14,69% de los EA son considerados graves. El 34,22% de los EA se consideraron evitables. Conclusiones: La prevalencia de EA en los pacientes de cirugía general y del aparato digestivo (CGAD) es elevada. La mayor parte de los EA fueron de tipo infeccioso. El EA más frecuente fue la infección de herida o sitio quirúrgico. Los pacientes con mayores grados de ASA, mayor complejidad y un tipo de ingreso urgente son factores asociados a la presencia de EA. La mayoría de los EA detectados han supuesto un daño leve o moderado sobre los pacientes. Alrededor de un tercio de EA fueron evitables.(AU)

Introduction: Knowledge of adverse events (AE) in acute care hospitals is a particularly relevant aspect of patient safety. Its incidence ranges from 3% to 17%, and surgery is related to the occurrence of 46%-65% of all AE. Material and methods: An observational, descriptive, retrospective, multicenter study was conducted with the participation of 31 Spanish acute-care hospitals to determine and analyze AE in general surgery services. Results: The prevalence of AE was 31.53%. The most frequent types of AE were infectious (35%). Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. The majority of patients (58.42%) were attributed a category F event (temporary harm to the patient requiring initial or prolonged hospitalization); 14.69% of AE were considered severe, while 34.22% of AE were considered preventable. Conclusions: The prevalence of AE in General and GI Surgery (GGIS) patients is high. Most AE were infectious, and the most frequent AE was surgical site infection. Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. Most detected AE resulted in mild or moderate harm to the patients. About one-third of AE were preventable.(AU)

Cascade Synthesis of New Indole-Containing Pentacyclic Scaffolds Mediated by Aryl and Iminyl Radicals.

A five-step approach, starting from simple 1,5-disubstituted indoles, has been implemented for the synthesis of diversely substituted indole-pyrido-indene pentacyclic compounds up to 54 % yield via domino radical-mediated processes in the presence of the radical reagents DLP/TTMSS and AIBN/TTMSS. Reactions proceeded with diverse key starting radical cyano-precursors strategically synthesized which were subsequently transformed into the target pentacyclic compounds through an aryl/iminyl radical-mediated domino reactions sequence. In addition to the routine spectroscopic techniques, the structure of radical precursors, as well as, the target pentacyclic products were unequivocally established by single crystal X-ray diffraction, confirming the effectiveness of the proposed synthetic sequence.

Analysis of adverse events in general surgery. Multicenter study.

INTRODUCTION: Knowledge of adverse events (AE) in acute care hospitals is a particularly relevant aspect of patient safety. Its incidence ranges from 3% to 17%, and surgery is related to the occurrence of 46%-65% of all AE. MATERIAL AND METHODS: An observational, descriptive, retrospective, multicenter study was conducted with the participation of 31 Spanish acute-care hospitals to determine and analyze AE in general surgery services. RESULTS: The prevalence of AE was 31.53%. The most frequent types of AE were infectious (35%). Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. The majority of patients (58.42%) were attributed a category F event (temporary harm to the patient requiring initial or prolonged hospitalization); 14.69% of AE were considered severe, while 34.22% of AE were considered preventable. CONCLUSIONS: The prevalence of AE in General and GI Surgery (GGIS) patients is high. Most AE were infectious, and the most frequent AE was surgical site infection. Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. Most detected AE resulted in mild or moderate harm to the patients. About one-third of AE were preventable.

Synthesis, Anticancer and Antitubercular Properties of New Chalcones and Their Nitrogen-Containing Five-Membered Heterocyclic Hybrids Bearing Sulfonamide Moiety.

A new series of sulfonamides, 8a-b, 10, 12, and 14a-b, were synthesized by N-sulfonation reaction with sulfonyl chlorides 6a-b. Five new series of chalcone-sulfonamide hybrids (16-20)a-f were prepared via Claisen-Schmidt condensation of the newly obtained sulfonamides with aromatic aldehydes 15a-f in basic medium. Chalcones substituted with chlorine at position 4 of each series were used as precursors for the generation of their five-membered heterocyclic pyrazoline (22-23)a-d, (24-25)a-b and carbothioamide 27a-f derivatives. The synthesized compounds were evaluated for their anticancer and antituberculosis activities. To determine their anticancer activity, compounds were screened against sixty human cancer cell lines at a single dose (10 µM). Compounds 17a-c were highly active against LOX IMVI (melanoma), with IC50 values of 0.34, 0.73 and 0.54 µM, respectively. Chalcone 18e showed remarkable results against the entire panel of leukemia cell lines with IC50 values between 0.99-2.52 µM. Moreover, compounds 20e and 20f displayed growth inhibition of Mycobacterium tuberculosis H37Rv at concentrations below 10 µM. Although they showed low selectivity in cytotoxicity tests against the Vero cell line, further optimization could advance the potential biological activity of the selected compounds.

Design and Synthesis of New Pyrimidine-Quinolone Hybrids as Novel hLDHA Inhibitors.

A battery of novel pyrimidine-quinolone hybrids was designed by docking scaffold replacement as lactate dehydrogenase A (hLDHA) inhibitors. Structures with different linkers between the pyrimidine and quinolone scaffolds (10-21 and 24−31) were studied in silico, and those with the 2-aminophenylsulfide (U-shaped) and 4-aminophenylsulfide linkers (24−31) were finally selected. These new pyrimidine-quinolone hybrids (24−31)(a−c) were easily synthesized in good to excellent yields by a green catalyst-free microwave-assisted aromatic nucleophilic substitution reaction between 3-(((2/4-aminophenyl)thio)methyl)quinolin-2(1H)-ones 22/23(a−c) and 4-aryl-2-chloropyrimidines (1−4). The inhibitory activity against hLDHA of the synthesized hybrids was evaluated, resulting IC50 values of the U-shaped hybrids 24−27(a−c) much better than the ones of the 1,4-linked hybrids 28−31(a−c). From these results, a preliminary structure−activity relationship (SAR) was established, which enabled the design of novel 1,3-linked pyrimidine-quinolone hybrids (33−36)(a−c). Compounds 35(a−c), the most promising ones, were synthesized and evaluated, fitting the experimental results with the predictions from docking analysis. In this way, we obtained novel pyrimidine-quinolone hybrids (25a, 25b, and 35a) with good IC50 values (<20 µM) and developed a preliminary SAR.

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study.

BACKGROUND: In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new "Trigger Tool" represents a sensitive predictor of adverse events in general surgery. METHODS: An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described "Trigger Tool" based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. RESULTS: The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The "Trigger Tool" had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the "Trigger Tool". CONCLUSIONS: The "Trigger Tool" has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies.

Design, synthesis, and molecular docking study of novel quinoline-based bis-chalcones as potential antitumor agents.

A novel series of quinoline-based symmetrical and unsymmetrical bis-chalcones was synthesized via a Claisen-Schmidt condensation reaction between 3-formyl-quinoline/quinolone derivatives with acetone or arylidene acetones, respectively, by using KOH/MeOH/H2 O as a reaction medium. Twelve of the obtained compounds were evaluated for their in vitro cytotoxic activity against 60 different human cancer cell lines according to the National Cancer Institute protocol. Among the screened compounds, the symmetrical N-butyl bis-quinolinyl-chalcone 14g and the unsymmetrical quinolinyl-bis-chalcone 17o bearing a 7-chloro-substitution on the N-benzylquinoline moiety and 4-hydroxy-3-methoxy substituent on the phenyl ring, respectively, exhibited the highest overall cytotoxicity against the evaluated cell lines with a GI50 range of 0.16-5.45 µM, with HCT-116 (GI50 = 0.16) and HT29 (GI50 = 0.42 µM) (colon cancer) representing best-case scenarios. Notably, several GI50 values for these compounds were lower than those of the reference drugs doxorubicin and 5-FU. Docking studies performed on selected derivatives yielded very good binding energies in the active site of proteins that participate in key carcinogenic pathways.

New thiazolyl-pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents.

A new series of N-substituted pyrazoline derivatives 6a-g, 7a-g, 8a-g, and 9a-g was synthetized by reaction of hydrazine derivatives and chalcone-thiazole hybrids bearing nitrogen mustard 5a-g. The chalcones 5a-g were obtained by Claisen-Schmidt condensation of thiazole-2-nitrogen mustard 3 and selected acetophenones 4a-g. These new compounds 6/7/8/9a-g were screened for their antifungal activity against Cryptococcus neoformans, with IC50 values of 3.9-7.8 µg/ml for the N-3,5-dichlorophenyl pyrazolines 9e-g. Interestingly, those compounds show low cytotoxic effects toward erythrocytes (RBC). In addition, N-acetyl (6a,b) and N-formyl pyrazolines (7a, 7b, 7c, and 7g) showed inhibitory activity against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, and vancomycin-intermediate S. aureus, with the most important minimum inhibitory concentration values ranging from 31.25 to 125 µg/ml. Regarding the antiprotozoal activity, thiazolyl-pyrazolines 9g, 8f, and 7c display high activity against Plasmodium falciparum, Leishmania (V) panamensis, and Trypanosoma cruzi, with EC50 values of 11.80, 6.46, and 4.98 µM, respectively, and with 7c being approximately 2.6-fold more potent than benznidazole with a selectivity index of 1.61 on U-937 human cells, showing promising potential as a novel antitrypanosomal agent.

Design of new quinolin-2-one-pyrimidine hybrids as sphingosine kinases inhibitors.

Sphingosine-1-phosphate is now emerging as an important player in cancer, inflammation, autoimmune, neurological and cardiovascular disorders. Abundance evidence in animal and humans cancer models has shown that SphK1 is linked to cancer. Thus, there is a great interest in the development new SphK1 inhibitors as a potential new treatment for cancer. In a search for new SphK1 inhibitors we selected the well-known SKI-II inhibitor as the starting structure and we synthesized a new inhibitor structurally related to SKI-II with a significant but moderate inhibitory effect. In a second approach, based on our molecular modeling results, we designed new structures based on the structure of PF-543, the most potent known SphK1 inhibitor. Using this approach, we report the design, synthesis and biological evaluation of a new series of compounds with inhibitory activity against both SphK1 and SphK2. These new inhibitors were obtained incorporating new connecting chains between their polar heads and hydrophobic tails. On the other hand, the combined techniques of molecular dynamics simulations and QTAIM calculations provided complete and detailed information about the molecular interactions that stabilize the different complexes of these new inhibitors with the active sites of the SphK1. This information will be useful in the design of new SphK inhibitors.

New chalcone-sulfonamide hybrids exhibiting anticancer and antituberculosis activity.

New sulfonamides 5/6 derived from 4-methoxyacetophenone 1 were synthesized by N-sulfonation reaction of ammonia (3) and aminopyrimidinone (4) with its sulfonyl chloride derivative 2. Sulfonamides 5 and 6 were used as precursors of two new series of chalcones 8a-f and 9a-f, which were obtained through Claisen-Schmidt condensation with aromatic aldehydes 7a-f. Compounds 5/6, 8a-d, 8f, 9a-d, and 9f were screened by the US National Cancer Institute (NCI) at 10 µM against sixty different human cancer cell lines (one-dose trial). Chalcones 8b and 9b satisfied the pre-determined threshold inhibition criteria and were selected for screening at five different concentrations (100, 10, 1.0, 0.1, and 0.01 µM). Compound 8b exhibited remarkable GI50 values ranging from 0.57 to 12.4 µM, with cytotoxic effects being observed in almost all cases, especially against the cell lines K-562 of Leukemia and LOX IMVI of Melanoma with GI50 = 0.57 and 1.28 µM, respectively. Moreover, all compounds were screened against Mycobacterium tuberculosis H37Rv, chalcones 8a-c and 9a-c were the most active showing MIC values between 14 and 42 µM, and interestingly they were devoid of antibacterial activity against Mycobacterium smegmatis and Staphylococcus aureus. These antituberculosis hits showed however low selectivity, being equally inhibitory to M. tuberculosis and mammalian T3T cells. The chalcone-sulfonamide hybrids 8a-f and 9a-f resulted to be appealing cytotoxic agents with significant antituberculosis activity.

Chloro-formyl steroids as precursors for hybrid heterosteroids: synthesis, spectroscopic characterization, and molecular and supramolecular structures.

Two new functionalized steroids containing both chloro and formyl substituents in ring A, and intended as precursors for the synthesis of hybrid systems, have been synthesized from ketosteroid precursors. 3-Chloro-2-formyl-17,17-dimethyl-18-nor-5α-androstane-2,13-diene, (I), and methyl 3-chloro-4-formyl-12-oxo-5ß-cholan-3-ene-24-oate, C26H37ClO4, (IV), have been synthesized using Vilsmeier reactions with 17ß-hydroxy-17α-methyl-5α-androstan-3-one and methyl 3,13-dioxo-5ß-cholan-24-oate, respectively. These products have been fully characterized using IR spectroscopy, 1H and 13C NMR spectroscopy, and high-resolution mass spectrometry, and in the case of (IV), a single-crystal X-ray diffraction study. Crystal structures have also been determined for the known analogues 3-chloro-2-formyl-17-oxo-5α-androst-2-ene, C20H27ClO2, (II), 3-chloro-2-formyl-5α-cholest-2-ene, C28H45ClO, (III), and the absolute and relative configurations are assigned for all four compounds (I)-(IV): when the fusion between rings A and B is trans, 3-chloro-2-formyl products are formed, but when this ring fusion is cis, a 3-chloro-4-formyl product results. The formation of (I) involves not only chloroformylation at ring A, but also dehydration and the 1,2 migration of a methyl group at ring D. In each of (II), (III) and (IV), rings B and C adopt almost perfect chair conformations, while ring A adopts a half-chair conformation. Ring D adopts an envelope conformation in each of (II) and (III), albeit differently folded in the two compounds, while in (IV), it adopts a half-chair conformation. A single C-H...O hydrogen bond links the molecules of (II) into C(6) chains which are linked into sheets by means of carbonyl-carbonyl interactions. The molecules of (IV) are linked into simple C(7) chains, again by a single C-H...O hydrogen bond, but there are no direction-specific interactions in (III) that are structurally significant.

Design of Two Alternative Routes for the Synthesis of Naftifine and Analogues as Potential Antifungal Agents.

Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, the γ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a ß-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5-7.8 µg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 µg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 µg/mL against C. neoformans.

A Schmidt rearrangement-mediated synthesis of novel tetrahydro-benzo[1,4]diazepin-5-ones as potential anticancer and antiprotozoal agents.

Novel tetrahydro-5H-benzo[e][1,4]diazepin-5-ones, several of them, containing the quinoline pharmacophore, were synthesized via a Schmidt rearrangement from their corresponding 1,2,3,4-tetrahydro-4-quinolones mediated by the NaN3/H2SO4 reaction conditions. Twelve of the obtained compounds were in vitro screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where compound 24a presented a remarkable activity against 58 of the 60 cancer cell lines, with the most important GI50 values ranging from 0.047 to 8.16 µM and LC50 values ranging from 9.4 to > 100 µM. Additionally, some of them were evaluated as antimalarial, antitrypanosomal and antileishmanial agents. The best antimalarial response was observed for compound 22g with an EC50 = 13.61 µg/mL for Plasmodium falciparum, while compound 24d exhibited high activity against Trypanosoma cruzi. and Leishmania (V) panamensis with EC50 = 2.78 µg/mL and 3.35 µg/mL respectively.

Microwave-Assisted Synthesis of Diversely Substituted Quinoline-Based Dihydropyridopyrimidine and Dihydropyrazolopyridine Hybrids.

An efficient, catalyst-free, and one-pot three-component procedure for the synthesis of novel and nitrogen rich dihydropyrido[2,3-d]pyrimidines and dihydro-1H-pyrazolo[3,4-b]pyridines bearing a quinoline pharmacophore fragment is provided. Reactions proceeded in DMF under microwave irradiation of three-component mixtures of formyl-quinoline derivatives, primary heterocyclic amines and cyclic 1,3-diketones. Interestingly, when conventional heating at reflux was used for the starting 5-amino-1-phenylpyrazole, the corresponding aromatized pyrazolopyridines were obtained as the main products. Single crystal X-ray analysis confirmed unequivocally the structure of both the dihydro- and aromatized products.

6-(Aryldiazenyl)pyrazolo[1,5-a]pyrimidines as Strategic Intermediates for the Synthesis of Pyrazolo[5,1-b]purines.

A microwave-assisted approach for the regioselective synthesis of functionalized 6-(aryldiazenyl)pyrazolo[1,5-a]pyrimidin-7-amines from the cyclization of 3-oxo-2-(2-arylhydrazinylidene)butanenitriles with 5-amino-1H-pyrazoles under solvent-free conditions has been developed. This methodology was distinguished by its broad substrate scope, operational simplicity, high atom economy, and high-yielding without requiring chromatographic purification. In addition, an efficient and versatile palladium-catalyzed reductive azo cleavage is disclosed for the synthesis of diverse heteroaromatic 1,2-diamines, a valuable synthetic building block to develop new fused heteroaromatic systems. As synthetic example, several substituted pyrazolo[5,1-b]purines were synthesized in yields up to 96% by using microwave irradiation in the cyclocondensation of these 1,2-diamines with orthoesters.

An efficient synthesis of new caffeine-based chalcones, pyrazolines and pyrazolo[3,4-b][1,4]diazepines as potential antimalarial, antitrypanosomal and antileishmanial agents.

A new series of chalcones 5a-f were synthesized from caffeine-based aldehyde 3 and substituted acetophenones 4a-f. Treatment of compounds 5a-f with hydrazine hydrate led to pyrazolines 6a-f, and their subsequent reaction with acetic anhydride or formic acid afforded the corresponding N-substituted pyrazolines 7a-f and 8a-f respectively. Additionally, the regioselective cyclocondensation reaction of chalcones 5a-f with 4,5-diaminopyrazole 9 afforded the diazepine derivatives 10a-f. Synthesis of the above novel compounds was carried out through a simple procedure involving an easy work-up and mild reaction conditions. In vitro antimalarial activity against Plasmodium falciparum was evaluated for the obtained compounds. Among of them, just pirazoline 6a showed an outstanding growth inhibition percentage 85.2 ± 5.4%, while diazepines 10a-f showed remarkable growth inhibitions in the range of 80.3 ± 13.5 to 94.2 ± 0.2% when were tested at 20 µg/mL. Compounds 5b, 5e, 7c and 7f showed remarkable activities against Leishmania panamensis with growth inhibition of 88.3 ± 1.5, 82.6 ± 2.2, 82.8 ± 1.7 and 87.6 ± 0.5% respectively, at 20 µg/mL. In vitro assays against Trypanozoma cruzi showed that pyrazoline 6d displayed a growth inhibition of 61.9 ± 7.8% at 20 µg/mL while chalcone 5f was considered especially active with a growth inhibition of 9.7 ± 1.5% for a very low concentration of 1.0 µg/mL.

A new series of antibacterial nitrosopyrimidines: synthesis and structure-activity relationship.

New nitrosopyrimidines were synthesized and evaluated as potential antibacterial agents. Different compounds structurally related with 4,6-bis(alkyl or arylamino)-5-nitrosopyrimidines were evaluated. Some of these nitrosopyrimidines displayed significant antibacterial activity against human pathogenic bacteria. Among them compounds 1c, 2a-c, and 9a-c exhibited remarkable activity against methicillin-sensitive and -resistant Staphylococcus aureus, Escherichia coli, Yersinia enterocolitica, and Salmonella enteritidis. A detailed structure-activity relationship study, supported by theoretical calculations, aided us to identify and understand the minimal structural requirements for the antibacterial action of the nitrosopyrimidines reported here. Thus, our results have led us to identify a topographical template that provides a guide for the design of new nitrosopyrimidines with antibacterial effects.

Synthesis and in vitro antitumor activity of a novel series of 2-pyrazoline derivatives bearing the 4-aryloxy-7-chloroquinoline fragment.

A new series of NH-pyrazoline derivatives 6 was synthesized by cyclocondensation reaction of novel [(7-chloroquinolin-4-yl)oxy]chalcones 5 with hydrazine hydrate. The treatment of pyrazolines 6 with acetic anhydride or formic acid yielded the N-acetyl- or N-formylpyrazoline derivatives 7-8, respectively. These novel 2-pyrazoline derivatives 6-8 were evaluated by the U.S. National Cancer Institute (NCI). Compounds 7b,d,f and 8c,f showed remarkable antitumor activity against 58 cancer cell lines, with the most important GI50 values from in vitro assays ranging from 0.48 to 1.66 µM. The 2-pyrazoline derivatives bearing the 4-aryloxy-7-chloroquinoline fragment are thus considered to be useful leads for the rational design of new antitumor agents.

Synthesis of novel polysubstituted (2SR,4RS)-2-heteroaryltetrahydro-1,4-epoxy-1-benzazepines and cis-2-heteroaryl-4-hydroxytetrahydro-1H-1-benzazepines as antiparasitic agents.

New series of polysubstituted (2SR,4RS)-2-heteroaryltetrahydro-1,4-epoxy-1-benzazepines and cis-2-heteroaryl-4-hydroxytetrahydro-1H-1-benzazepines were designed and synthesized in moderate to high yields using a three-step procedure from ortho-allylanilines. Their antiparasitic activity was evaluated against the extracellular and intracellular forms of Trypanosoma cruzi and Leishmania (Leishmania) infantum parasites. Their cytotoxicity was also determined on Vero and THP-1 mammalian cells. Many of the tested compounds inhibited significantly the growth of extracellular forms of T. cruzi and L. (L.) infantum without showing cytotoxicity on Vero and HTP-1 cells. Only compounds 10h and 14f demonstrated good activity against amastigotes of T. cruzi, but none was able to inhibit the growth of L. (L.) infantum amastigotes.

Highly efficient and diastereoselective synthesis of new pyrazolylpyrrolizine and pyrazolylpyrrolidine derivates by a three-component domino process.

Diastereoselective reactions between 4-formylpyrazoles, N-substituted maleimides and glycine derivates led to new series of pyrazolyldipyrrolo [3,4-a:3',4'-f]pyrrolizines and pyrazolylpyrrolo[3,4-c]pyrroles in good yields. The reactions proceeded by a domino process through azomethine ylides formed in situ via a 1,3-dipolar cycloaddition reaction.