The synthesis of the compounds [(7-chloroquinolin-4-yl)amino]acetophenones (4, 5) and their copper(II) complexes (4a, 5a) is reported. The compounds were characterized using a wide range of spectroscopic and spectrometric techniques, such as FTIR, UV-vis, NMR, EPR, ESI-CID-MS2. The spectral results suggested that the ligand acted as chelating species coordinating the metal through the endocyclic nitrogen of the quinoline ring in both complexes, with general formulae expressed in two ways, according to the phase in which they are: [Cu(L)2Cl2] for solid phase and [Cu(L)2][2Cl] for liquid phase. The EPR study of the Cu (II) complexes indicated a probable distorted tetrahedral coordination geometry. This result was confirmed by the calculated optimized structures at the DFT/B3LYP method with the 6-31G (d,p) basis set. The characterization of the fragmentation pattern of protonated free ligands was extended here to fragments as low as m/z 43, while for coordination complexes it extends to fragments at m/z 80 and m/z 111. The antimalarial activity of the compounds was determined through three different tests: inhibitory activity against in vitro growth of Plasmodium falciparum (W2), inhibition of hemozoin formation (β-hematin) and in vitro inhibitory activity against recombinant falcipain-2, where compound 5 showed considerable activity. However, the activity of free ligands against P. falciparum was increased by complexing with the Cu (II) metal ion. The values of the HOMO-LUMO energy gap of 3.847 eV (4a) and 3.932 eV (5a) were interpreted with high chemical activity and thus, could influence on biological activity. In both compounds, the total electron density surface mapped with electrostatic potential clearly revealed the presence of high negative charge on the Cu atom. Also, this study reported the molecular docking of free ligands (4, 5) using software package ArgusLab 4.0.1. The results revealed the importance of water molecules as interaction bridges through hydrogen bonds between free ligands and β-hematin; at the same time, the hypothesis that π-π interaction between quinoline derivatives and the electronic system of hematin governs the formation of adducts was confirmed.

This study describes the synthesis, characterization and antimicrobial activity evaluation of 2-(1-{3-[(7-chloroquinolin-4-yl)amino]phenyl}ethylidene)hydrazinecarboxamide (5), which was designed and synthesized applying a molecular hybridization strategy, considering two pharmacophoric portions: 7-chloro-4-aminoquinoline and semicarbazone; both fractions have been related to antimicrobial activity exhibited by a series of derivatives synthesized. Compound 5 was characterized using 1H NMR, 13C NMR and Electrospray Ionization Mass Spectrometry (ESI-MS) studies. Biological evaluation showed that compound 5 exhibited antimicrobial activity against bacteria Gram (-) Pseudomona aeruginosa, comparable with the activities corresponding to Amikacin, Ampicillin/Sulbactam and Ofloxacin.

La quimica como ciencia no deja de sorprender con sus nuevos descubrimientos y, mas aun, cuando se piensa que todas las teorias cientificas estan completamente descritas. El objetivo del presente estudio fue describir como se debe ensenar, en el contexto educativo, el nuevo descubrimiento de la hexavalencia del atomo de carbono. Se aplico la ruta epistemologica racional deductiva, utilizando el metodo del analisis de contenido para derivar una matriz de caracterizacion, donde se realiza la descripcion del carbono tetravalente y hexavalente. Entre las conclusiones mas resaltantes del estudio se tiene que la ensenanza de la hexavalencia del atomo de carbono debe ser incluida en la episteme de docentes y estudiantes, mediante la aplicacion de estrategias que permitan comprender la posibilidad del atomo de carbono de formar mas de cuatro enlaces en los compuestos organicos.

El objetivo del estudio fue caracterizar las estrategias didacticas durante el proceso de validacion del modelo teorico de relacionales funcionales entre la practica pedagogica y generacion de conocimiento cientifico. La investigacion fue de tipo documental fundamentandose en las siguientes consideraciones: se utilizo el metodo deductivo como metodo de abordaje. Para recoger los datos se siguio el procedimiento del analisis en cadena, considerado en la logica formal, cuya tecnica es la observacion directa de los registros de las caracteristicas esenciales del objeto del estudio, en este caso las estrategias didacticas que permiten leer los constructos teoricos de las relacionales funcionales entre la practica pedagogica y generacion de conocimiento cientifico. Entre las conclusiones se tiene que la conversion de los constructos teoricos de las funciones relacionales del modelo axiomatico en conceptos empiricos requiere de estrategias para su operacionalizacion las cuales deben presentar relaciones univocas con los aspectos epistemologicos.

A simple synthesis and study by UV-vis, IR, NMR, ESI-CID-MS2 and X-ray diffraction of ((2E)-2-(1-{4-[(7-chloroquinolin-4-yl)amino]phenyl}ethylidene)hydrazinecarbothioamide is reported. It was tested in vitro against chloroquine-resistant strain (W2) of Plasmodium falciparum, hemozoin (β-hematin) formation and cysteine protease falcipain-2. In general, it was found to possess a proved activity in its inhibitory power on the parasite but less active on the formation of hemozoin (β-hematin) and falcipain-2. Also, the X-ray analysis presented an unexpected electronic density that can be assigned like S(2). This electronic density can be attributed to autocondensation of thiosemicarbazide, generating H2S as a subproduct. DOI: http://dx.doi.org/10.17807/orbital.v9i4.1001

La malaria o paludismo continua representando una de las mayores causas de morbilidad y mortalidad en el mundo, a pesar de haber sido combatida por una variedad de medicamentos. La revision que a continuacion se presenta tiene un proposito orientador y educativo para cualquier investigador que se inicie en el diseno, sintesis y evaluacion de potenciales antimalaricos. Con esta revision se pretende hacer un repaso de los principales farmacos empleados en la quimioterapia antimalarica desde sus inicios hasta la actualidad, haciendo enfasis en los posibles mecanismos de accion involucrados y resaltando la importancia del estudio de nuevos blancos o dianas para el desarrollo de moleculas lideres que puedan lograr solventar el problema de la resistencia a multiples farmacos desarrollada por el parasito. Finalmente, se presentan las perspectivas a futuro que investigadores de diversas areas proponen para continuar reforzando la quimioterapia antimalarica. Palabras clave: malaria, antimalaricos, blancos moleculares, resistencia a drogas. Malaria (paludism) continues to represent a major cause of morbidity and mortality across the world, despite being combated by several antimalarial drugs. The review presented below have a guiding and educational purpose for any researcher that starts in the design, synthesis and evaluation of potential antimalarials. In this review, we will focus in main drugs used in malaria chemotherapy and mechanism of drug action, highlighting well known and newly discovered potential antimalarial drug targets for developing lead molecule, to rectify the increasing problem of parasitic multidrug resistance. Finally, a future perspective will be presented based on proposals to further strengthen antimalarial chemotherapy. Keywords: malaria, antimalarials, molecular targets, drug resistance

Amaranth species are gaining increasing interest for human and animal nutrition, although its use is limited due to their toxic and antinutritional substances contents. The contents of toxic and antinutritionals substances (oxalates, phytates, total phenols, condensate tannins, hydrolysable tannins and cyanide) in the leaves, stems, and panicles of Amaranthus dubius Mart. ex Thell., not yet investigated, were evaluated in both rainy and dry seasons. The plants were cultivated in El Nectar Hacienda, located in Merecure, in the municipality of Acevedo, Miranda State, Venezuela (10 degrees 31'38" N, 66 degrees 33'16" W). The concentration of oxalates, phytates, total phenols, condensate and hydrolysable tannins were determined by classic colorimetric techniques, the cyanide being determined by silver nitrate titration. The content of toxic and antinutrients in A. dubius ranged from 169.6 to 368.5 mg of oxalates. kg(-1) DM, 0.771 to 7.482 mg of phytates. g(-1) DM, 0.47 to 1.77 mg of total phenols. g(-1) DM, and 0.22 to 1.20 mg of condensate tannins. g(-1) DM. Cyanide and hydrolysable tannins were not detected. The values of most of these substances presented differences according to harvesting seasons and plant part (P<0.001), as well as an interaction between both factors. The content of toxic and antinutrients was generally higher in the dry than in the rainy season for all parts of the plant. The harvesting season and the plant part affect the content of toxic and antinutritional substances in A. dubius, whose values were, however, below the maximum levels allowed by regulators for human consumption. Therefore, as raw material it does not need to be processed in order to guarantee its harmlessness.

En las ultimas decadas son muchos los compuestos con actividad dopaminergica central que se han disenado, sintetizado y evaluado farmacologicamente. A pesar de ello, no se ha logrado obtener un farmaco capaz de mejorar o curar las patologias que involucran la regulacion dopaminergica en el sistema nervioso central tales como la Enfermedad de Parkinson y la esquizofrenia, entre otras. Tomando en consideracion el termino de “farmacoforo atipico” y a partir del compuesto 5 , se incorporo el fragmento aralquil y se sintetizaron los compuestos 10, 11, 13a-h y 14a-h . Tanto los compuestos 10 y 13a-h bajo su forma metoxilada como los compuestos 11 y 14a-h bajo su forma fenolica, fueron evaluados farmacologicamente para determinar su actividad agonistica y antagonistica sobre el sistema dopaminergico central. Para ello se determino el efecto de la inyeccion intracerebroventricular de dichos compuestos sobre el balance hidromineral y la conducta estereotipada en ratas. Los resultados de la evaluacion farmacologica preliminar muestran una accion central a traves de mecanismos dopaminergicos, siendo que los compuestos 10, 11, 13d-h y 14a mostraron respuestas como agonistas, mientras que los compuestos 14b-h , tuvieron respuestas como antagonistas

CONTEXT:Characterization of the pro-oxidant activity of QNACR.OBJECTIVES:Reactive oxygen species (ROS) induce cellular damage and represent unique opportunities to kill malignant cells. In this study, we synthesized and evaluated the new compound, (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate (QNACR) as potential pro-oxidative agent against breast cancer.METHODS:Oxidative stress biomarkers such as ROS, thiobarbuturic acid reactive species (TBARs) and different antioxidant enzyme activities were determined in cell lysates.RESULTS:QNACR showed cytotoxic and more selective effects to tumour MCF7 cells (IC50 < 25 µM) compared to antitumour controls, inducing ROS and TBARs parallel to inhibitions of catalase (CAT), glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH). Longer exposures to QNACR triggered adaptive effects increasing the overall activities of CAT, glutathione reductase, G6PDH and 6PGDH, but eventually the adaptation changes faded and cells died.CONCLUSION:QNACR led to remarkable modifications in the oxidative status of tumour cells, proposing this compound as potential alternative for antitumour therapy.

Amaranth (Amaranthus dubius Mart. ex Thell.) is used as forage in the diet of sheep, goats, pigs and cattle, and is also reported as weed in various commercial crops. Its metal content was evaluated in leaves, stems and panicles of plants collected in the rainy and dry seasons. The plants were grown in the town of Merecure, Acevedo Municipality, Miranda state, Venezuela. The concentration of Ca, Mg, Zn, Fe, Cu, Al, Cd, Pb and Hg were evaluated by atomic absorption spectroscopy, and Na and K by flame photometry. The values found were higher than those reported in other studies in the same as well as other species of amaranth. The major metals were Ca, K, Al, Mg and Fe. Traces of Hg were detected, while the presence of Cd and Pb was not detected. Metal accumulation differed among plant organs, and was influenced by the collection season when.

Quinolines and acrylates are chemical compounds which were previously described as potential antitumor agents. In this study, a series of seven new quinolinyl acrylate derivatives were synthesized and evaluated against human prostate cancer cells PC-3 and LNCaP in vitro and in vivo. The most effective compound (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4 hydroxyphenyl) acrylate reduced the viability in both cell lines in a time- and dose-dependent manner. Inhibitory effects were also observed on the adhesion, migration, and invasion of the prostate cancer cells as well as on the neoangiogenesis, clonogenic and MMP-9 activity. The effect in vivo was studied in PC-3 xenografts in nude mice. The results were concordant with the in vitro effects and showed decreased tumor growth in treated animals compared to controls. The study suggests the multi-target efficacy of the quinolinyl derivate against human prostate cancer cells and supports its potential therapeutic usefulness.

Resumen es: Los avances alcanzados con la aplicacion de los diferentes metodos espectroscopicos han representado una de las armas fundamentales en el diseno racional...

El amaranto (Amaranthus dubius Mart. ex Thell.) es utilizado como planta forrajera en la alimentacion de ovinos, caprinos, porcinos y bovinos, ademas, de ser reportada como arvense en diversos cultivos comerciales. Se evaluo el contenido de metales en hojas, tallos y paniculas de amaranto recolectado en epoca lluviosa y seca. Las plantas fueron cultivadas en la poblacion de Merecure, municipio Acevedo, estado Miranda, Venezuela. Se determino la concentracion de Ca, Mg, Zn, Fe, Cu, Al, Cd, Pb y Hg por espectroscopia de absorcion atomica y Na y K por fotometria de llama. Los valores encontrados fueron superiores a los reportados por otros investigadores en la misma y en otras especies de amaranto. Los metales mayoritarios fueron Ca, K, Al, Mg y Fe. Se detecto trazas de Hg y no se evidencio la presencia de Cd y Pb. La acumulacion de metales fue heterogenea entre los organos de la planta y estuvo influenciada por la epoca de recolecta.

[(7-Chloroquinolin-4-yl)amino]chalcone derivatives derived from the corresponding 3- or 4-[(7-chloroquinolin-4-yl)amino]acetophenone were synthesized and evaluated for in vitro antimalarial and anticancer activity. The most active compounds 12, 13, 15, 17 and 19 from the 3-substituted series displayed inhibitory values against heme cristallization in the range of 93.14 ± 1.74 – 94.93 ± 1.50 % as an antimalarial mechanism and cytotoxic effect with IC50 values of 7.93 ± 2.05, 7.11 ± 2.06 and 6.95 ± 1.62 μg/mL for 13, 17 and 19 respectively against humane prostate LNCaP tumor cells.

[(7-Chloroquinolin-4-yl)amino]chalcone derivatives derived from the corresponding 3- or 4-[(7-chloroquinolin-4-yl)amino]acetophenone were synthesized and evaluated for in vitro antimalarial and anticancer activity. The most active compounds 12, 13, 15, 17 and 19 from the 3-substituted series displayed inhibitory values against heme cristallization in the range of 93.14 ± 1.74 – 94.93 ± 1.50 % as an antimalarial mechanism and cytotoxic effect with IC50 values of 7.93 ± 2.05, 7.11 ± 2.06 and 6.95 ± 1.62 μg/mL for 13, 17 and 19 respectively against humane prostate LNCaP tumor cells.

A series of thieno[2,3-b]quinolone derivatives were synthesized and investigated for their abilities to inhibit beta-hematin formation, hemoglobin hydrolysis and in vivo for their efficacy in rodent Plasmodium berghei. Compound 3b was the most promising as inhibitor of hemoglobin hydrolysis, and its effects as inhibitor of P-hematin formation was promising. When the aromatic ring was substituted in 2 (Me), in 3 (CF3) or in 2,4 (Cl) the inhibition of hemoglobin proteolysis was maximal (88%), the rest of compounds maintained a low inhibition. The most active compound to emerge in vitro and in murine studies, was 3b suggesting an antimalarial activity via multiple mechanisms.

A series of (E) 2-quinolinylmethylidene-5,7-dimethoxyindanones were prepared via base catalyzed Claisen-Schmidt condensation of 5,7-dimethoxy-1-indanone with the appropriate 2-chloro-3-formylquinoline derivative. Evaluation of their in vitro inhibition of beta-hematin formation and hemoglobin hydrolysis and in vivo efficacy in rodent Plasmodium berghei suggest the antimalarial activity is derived from inhibition of hemoglobinolytic proteases.

Various substituted benzothiazole-6-carboxylic acids (4a–i) have been prepared by the condensation of 4-amino-3-mercaptobenzoic acid and aldehydes in nitrobenzene as oxidant. Compound 4i was found to be a good candidate as an inhibitor of β-hematin formation in vitro.

The X-ray crystal structure of 7-chloro-3-amino-9-(4-bromophenyl)thieno-[3,2-b]benzothiazine 4,4-dioxide 2-carboxylate 1 is determined. The thiophene ring and the exocyclic ester group adopt a co-planar conformation, which is stabilised by an intramolecular hydrogen bond. The moderate antimalarial activity shown by this compound appears to be related to the formation of such an intramolecular N–H···O =C hydrogen bond.