Revista Colombiana de Ciencias Químico - Farmacéuticas

Dos distúrbios psiquiátricos à antibioticoterapia: reposicionamento da clorpromazina como agente antibacteriano

RESUMO O alarmante aumento na taxa de resistência aos antibióticos põe em check à eficácia da terapia antibacteriana futura. Em contrapartida, as indústrias farmacêuticas negligenciam os investimentos em pesquisa e desenvolvimento de novos fármacos antimicrobianos em virtude de questões financeiras, legais e farmacológicas. Assim sendo, o reposicionamento de agentes disponíveis clinicamente torna-se uma promissora ferramenta para tentar driblar o desinteresse das indústrias. O fármaco antipsicótico clorpromazina (CPZ) destaca-se por possuir uma ampla faixa de atividade antibacteriana, a qual cobre desde patógenos Gram-positivos e Gram-negativos, até as mico-bactérias. A atividade antibacteriana é independente do perfil de susceptibilidade do microrganismo, sendo ela mantida mesmo em cepas altamente resistentes aos antibióticos. Alguns estudos mostram que mesmo nas concentrações clinicamente disponíveis no plasma (entre 0,1-0,5 (g/mL), a CPZ é capaz de matar Staphylococcus aureus e Mycobacterium tuberculosis dentro dos macrófagos. Em adição, estudos clínicos têm revelado os benefícios do uso da CPZ na terapia de suporte para pacientes com infecções em curso. Em conclusão, a CPZ pode eventualmente ser direcionada ao arsenal terapêutico antimicrobiano, especialmente no manejo das infecções causadas por microrganismos intracelulares com fenótipo multirresistente.

SUMMARY The substantial increase in the antibiotic resistance brings on an alarm to the future of the antibiotic therapy. However, the pharmaceutical industry has been neglecting its investments in new drug research and development, mainly because of the pharmacologic, financial and legal factors. Therefore, the drug repositioning of clinic available agents become a promising tool to bypass the lack of interest of the pharmaceutical industry. A drug used to treat psychoses, the Chlorpromazine (CPZ), stands out as a large spectrum antibiotic, which covers Gram-positive and Gram -negative bacteria, and also mycobacteria. Its antibacterial activity is not related to microorganism susceptibility profile, and it could be maintained even on strains highly resistant to the conventional antibiotics. Studies point out that even on serum concentrations clinically available, the CPZ can eliminate Staphylococcus aureus and Mycobacterium tuberculosis inside of macrophages. In addition, clinical trials have revealed its benefits on support therapy for patients suffering from active infections. As a result, the CPZ could be used as an optional antibiotic therapy, especially in case of infections due to intracellular microorganisms with multidrug resistance phenotype.

Utilização dos métodos automáticos em fluxos com detecção espectrofotométrica na determinação de diclofenaco de sódio em formulações farmacêuticas e fluidos corporais

RESUMO Este trabalho descreveu e comparou quatro estudos entre si que utilizaram métodos automáticos em fluxo com detecção espectrofotométrica e a reação de oxidação do diclofenaco para determinar diclofenaco em formulações farmacêuticas e fluidos corporais. Para isso, utilizamos os seguintes artigos: Versatility of a multicommuted flow system in the spectrometric determination of three analytes, Sequential injection spectrophotometric method for the assay of anti-inflammatory diclofenac sodium in pharmaceutical preparations, Screening of conditions controlling spectrophotometric sequential injection analysis e Sequential injection spectrophotometric determination of diclofenac in urine and pharmaceutical formulations e detalhamos as metodologias empregadas, os resultados, conclusões obtidas e comparamos entre eles os limites de detecção, desvio padrão relativo e a frequência analítica. Os resultados mostraram diferenças significativas entre métodos empregados e a utilização do Sistema automático do tipo Análise por Injeção Sequencial, apesar deste possuir menor frequência analítica.

SUMMARY This study described and compared four studies that used automatic flow methods with spectrophotometric detection and the oxidation reaction of diclofenac to determine diclofenac in pharmaceutical formulations and body fluids. For this, the following articles were used: Versatility of a multicommuted flow system in the spectrometric determination of three analytes, Sequential injection spectrophotometric method for the assay of anti-inflammatory diclofenac sodium in pharmaceutical preparations, Screening of conditions controlling spectrophotometric sequential injection analysis and Sequential injection spectrophotometric determination of diclofenac in urine and pharmaceutical formulations and we detail the methodologies used, the results, the conclusions obtained and compare the limits of detection, relative standard deviation and analytical frequency. The results showed significant differences between the employed methods and the use of the Automatic System of the Sequential Injection Analysis type, although this one has a lower analytical frequency.

Theoretical study of compounds derived from cephalosporins with inhibitory activity potential front to penicillin binding proteins (PBP) and resistance to Extended spectrum Beta-lactamase (ESBL) produced by Escherichia coli

RESUMEN Se han utilizado herramientas computacionales para proponer moléculas derivadas de cefalosporinas con potencial actividad antibacteriana, frente a cepas de Escherichia Coli, con mayor afinidad como inhibidores de enzimas de unión a penicilinas y que a su vez disminuyan o no tengan afinidad por betalactamasas de espectro extendido. Se diseñaron 20 moléculas con base en la estructura molecular de la cefalosporina, las estructuras fueron optimizadas utilizando la teoría del funcional de la densidad, se calcularon descriptores moleculares de reactividad, de forma paralela se sometieron a acoplamiento molecular con las enzimas antes mencionadas. Las moléculas presentaron valores de energía de unión negativos, doce moléculas mostraron una orientación e interacciones favorables en el sitio activo de la enzima de unión a penicilinas y trece moléculas presentaron menor afinidad que el ligando nativo (cefotaxima) por la betalactamasa. Tres moléculas pueden considerarse como potenciales inhibidores de enzimas de unión a penicilinas resistentes y betalactamasas.

SUMMARY Computational tools have been used to propose molecules derived from cephalosporins with potential antibacterial activity, against strains of Escherichia Coli, with higher affinity as inhibitors of penicillin-binding enzymes and which in turn decrease or do not have affinity for extended-spectrum beta-lactamases. 20 molecules were designed based on the molecular structure of the cephalosporin, the structures were optimized using the density functional theory, molecular descriptors of reactivity were calculated, and in parallel form they were subjected to molecular docking with the enzymes mentioned above. The molecules showed negative binding energy values, 12 molecules showed an orientation and favorable interactions in the active site of the penicillin binding enzyme and thirteen molecules had lower affinity than the native ligand (Cefotaxime) for betalactamase. Three molecules can be considered as potential inhibitors of binding enzymes to resistant penicillins and betalactamases.

Phytochemical study of leaves of Cavendishia compacta (Ericaceae) and evaluation of its anti-inflammatory activity

RESUMEN Se realizó el estudio fitoquímico de hojas de Cavendishia compacta. La separación de extractos y fracciones por cromatografías en columna, capa delgada y capa delgada preparativa, permitieron obtener una mezcla de diterpenos conformada por kaurano, rimuneno y biformeno; una mezcla de compuestos aromáticos constituida por acetofenona y benzaldehído; una mezcla de triterpenos constituida por α-amirina y β-amirina y el aislamiento de morina y miricetina. La actividad antiinflamatoria se evaluó al extracto etanólico y las fracciones de hexano, dicolorometano y acetato de etilo, utilizando el modelo de edema auricular inducido por TPA, siendo el extracto etanólico y la fracción de dicolorometano los que presentaron un efecto antiinflamatorio moderado de 49,3% y 39,8% respectivamente.

Summary The phytochemical study of leaves of Cavendishia compacta was carried out. The separation of extracts and fractions by column chromatography, thin layer and preparative thin layer allowed to obtain a mixture of diterpenes consisting of kaurane, rimunene and biformene; a mixture of aromatic compounds constituted by acetophenone and benzaldehyde; a mixture of triterpenes constituted by α -amirine and β-amirin and the isolation of morine and myricetin. The anti-inflammatory activity was evaluated to the ethanolic extract and fractions of hexane, dichloromethane and ethyl acetate using the model of atrial edema induced by TPA, being the etha-nolic extract and the fraction of dicholoromethane those that presented a moderate anti-inflammatory effect of 49.3 % and 39.8% respectivel.

Essential oils as a source of bioactive molecules

SUMMARY Nature gives us a large number of compounds with interesting biological properties, within them we have essential oils, which are an important source of new bioactive molecules, which can replace synthetic chemicals, since they are friendly to the environment and they are less toxic. Currently there are more than 20.000 publications in which essential oils are related to some biological activity, according to the search made in different databases until January 2018. This confirms the wide utility of essential oils as the main source of bioactive metabolites, which can be used in different areas of our life.

RESUMEN La naturaleza nos proporciona una gran cantidad de compuestos con interesantes propiedades biológicas, dentro de los cuales tenemos los aceites esenciales, los cuales son una fuente importante de nuevas moléculas bioactivas, que pueden reemplazar a los químicos sintéticos, ya que son amigables con el medio ambiente y son menos tóxicos. Actualmente existen más de 20.000 publicaciones en las que los aceites esenciales están relacionados con alguna actividad biológica, según la búsqueda realizada en diferentes bases de datos hasta enero de 2018. Esto confirma la amplia utilidad de los aceites esenciales como principal fuente de metabolitos bioactivos, que pueden ser utilizados en diferentes áreas de nuestra vida.

Effect of dry chloroformic and dichloromethane extracts of Tropaeolum tuberosum (Ruiz & Pavón) mashua on seminal parameters and acute toxicity

RESUMEN Con el objetivo de demostrar el efecto de los extractos secos clorofórmico y de diclorometano de Tropaeolum tuberosum R&P mashua sobre los parámetros seminales y su toxicidad aguda en ratones albinos, se utilizó dos grupos experimentales y un grupo control. Los ratones fueron sacrificados, después de 7 días, luego de recibir los dos tipos de extractos, realizando posteriormente el conteo de espermatozoides utilizando la cámara y el método de Neubauer. Los extractos aplicados por vía intraperitoneal, afectaron la cantidad de espermatozoides en ratones, obteniendo: que el grupo que recibió el extracto clorofórmico presentó disminución del 79,9% en el número de espermatozoides y el grupo con diclorometano presentó disminución del 77,1%, ambos con respecto al grupo control.

SUMMARY With the goal of proving the effect of chloroformic and dichloromethane dry extracts from Tropaeolum tuberosum R& P mashua, on the seminal parameters and its acute toxicity in albino mice. It was used two experimental groups and a control group. The mice were sacrificed, after 7 days while they were receiving the two kinds of extracts, making after that a sperm count, using for that the Neubauer's method and camera. The extracts, applied intraperitoneally, affect the amount of sperm on mice, getting: The group that received the chloroform extract showed a 79.9% decrease in the number of spermatozoids and the group that received the dichloromethane extract showed a decrease of 77.1%, both with respect to the control group.

Avaliação da toxicidade e atividade moluscicida do óleo essencial Cinnamomum zeylanicum Blume contra o caramujo Biomphalaria glabrata (Say, 1818)

RESUMO Este trabalho determina a toxicidade e o efeito moluscicida do óleo extraído das folhas de Cinnamomum zeylanicum Blume contra o caramujo Biomphalaria glabrata (Say, 1818). Para isso, o óleo essencial foi extraído quantitativamente por hidro-destilação. Em seguida, quantificações de seus componentes foram realizadas por cromatografia gasosa acoplada a espectrometria de massas (CG-MS) e a toxicidade e atividade moluscicida do óleo foram testadas, respectivamente, contra Artemia salina e caramujos Biomphalaria glabrata (Say, 1818). A concentração letal (CL50) foi calculada a partir dos métodos Reed-Muench & Pizzi, respectivamente, para toxicidade e teste moluscicida. Os resultados das análises cromatográficas mostraram que o óleo possui 83% de eugenol (constituinte majoritário) e 2,5% de humuleno (componente minoritário). Na avaliação de toxicidade, o óleo foi considerado moderadamente tóxico com uma CL50 de 162,1 mg.L-1 ± 2,80, com intervalo de confiança de 95%, enquanto a atividade moluscicida apresentou concentração letal de 50% (CL50) de 18,62 mg.L-1 ± 2,18, com intervalo de confiança de 95%. Portanto, o óleo é ativo contra o caramujo Biom-phalaria glabrata.

SUMMARY This work determines the toxicity and the molluscicidal effect of the oil extracted from the leaves of Cinnamomum zeylanicum Blume against the snail Biomphalaria glabrata (Say, 1818). For this, the essential oil was extracted quantitatively by hydrodistillation. Then, quantifications of its components were performed by gas chro-matography coupled to mass spectrometry (CG-MS) and the toxicity and mollus-cicidal activity of the oil were tested, respectively, against Artemia salina and snails Biomphalaria glabrata (Say, 1818). The lethal concentration (LC50) was calculated from the Reed-Muench & Pizzi methods, respectively, for toxicity and molluscicide testing. The results of the chromatographic analysis showed that the oil has 83% eugenol (majority constituent) and 2.5% humulene (minority component). In the toxicity evaluation, the oil was considered to be moderately toxic with a LC50 of 162.1 mg.L-1 ± 2.80, with a 95% confidence interval, while the molluscicidal activity presented a lethal concentration of 50% (LC50) of 18.62 mg. L-1 ± 2.18, with a 95% confidence interval. Therefore, the oil is active against the snail Biomphalaria glabrata.

Self-medication in the students from Neiva Campus of the Universidad Cooperativa de Colombia

RESUMEN La automedicación es una práctica riesgosa cuyas consecuencias incluyen enmascaramiento de una enfermedad, aparición de reacciones adversas, interacciones medicamentosas, aumento de la resistencia a ciertos tipos de fármacos y fármaco dependencia. La Organización Mundial de la Salud contempla la posibilidad de educar a la población en prácticas de automedicación responsable, señalando al profesional farmacéutico como figura clave de este proceso educativo. El presente trabajo analiza las conductas de automedicación en una población encuestada de 600 estudiantes de la Universidad Cooperativa de Colombia Campus Neiva. Los resultados de la encuesta han sido analizados en forma global y diferenciando a los encuestados en subgrupos de: a) programa académico y b) variables sociodemográficas. Los resultados indican que la automedicación es una práctica común en estudiantes de la Universidad Cooperativa de Colombia Campus Neiva que no siempre se lleva a cabo de acuerdo con las recomendaciones de la OMS para poder considerarse una práctica responsable y segura.

SUMMARY Self-medication is a dangerous practice with consequences including masking of disease, adverse reactions to medications, drug interaction, resistance to certain types of therapeutic agents and drug dependence. The World Health Organization has considered the possibility of educating population in practices of responsible self-medication, pointing at the pharmacist as a key figure in this educational process. In the present work we have analyzed the self-medication conducts of 600 surveyed college students of the Universidad Cooperativa de Colombia Sede Neiva (UCC). The overall results of the survey have been analyzed; we have also divided the surveyed population in subgroups of: a) Academic program and b) Sociodemographic variables. Results indicate that self-medication is a common practice among college students of UCC, and that it is not always practiced according to WHO recommendations for responsible, safe self-medication.

CdCl₂ has zero-order kinetic cellular influx and induces cytotoxicity and genotoxicity at low concentrations in human leukocytes in vitro

SUMMARY Cadmium (Cd2+) is a nonessential heavy metal that possesses a high capacity of bioaccumulation and exhibits toxic characteristics even at low concentrations. This study evaluated the genotoxicity and cytotoxicity in human leukocytes in vitro after exposure to a lower range of Cd2+concentration (1-25 (g/mL) using an unprecedented strategy by correlating between intracellular Cd2+ levels after exposure and cellular damage. Results demonstrated that Cd2+exposure from 5 to 25 fig/mL significantly increased the unviability of leukocytes, as well as the DNA damage, which was dose-dependent. The intracellular Cd2+ levels in leukocytes ranged from 9.85 to 94.38 pg/cell, and cytotoxicity and genotoxicity were induced at a concentration of24.22 pg/cell. The relationship between exposure concentration and intra-cellular Cd2+ levels suggests that its influx occurs in human leukocytes under zero-order kinetics.

RESUMEN El cadmio (Cd2+) es un metal pesado no esencial que posee una alta capacidad de bioacumulación y presenta características tóxicas incluso en bajas concentraciones. Este estudio evaluó la genotoxicidad y la citotoxicidad en leucocitos humanos in vitro después de la exposición a un rango inferior de concentración de Cd2+ (1-25 (g / mL) mediante una estrategia sin precedentes al correlacionar los niveles intracelulares de Cd2+ después de la exposición y el daño celular. Los resultados demostraron que la exposición a Cd2+ de 5 a 25 (g/mL aumentó significativamente la inviabilidad de los leucocitos, así como el daño en el ADN, que era dependiente de la dosis. Los niveles intracelulares de Cd2+ en leucocitos oscilaron entre 9,85 y 94,38 pg/célula, y se indujo la citotoxicidad y la genotoxicidad a una concentración de 24,22 pg/ célula. La relación entre la concentración de la exposición y los niveles intracelulares de Cd2+ sugiere que su influjo se produce en leucocitos humanos bajo una cinética de orden cero.

A descrição matemática do processo da detecção eletroquímica do ácido ascórbico sobre o polímero condutor, dopado pelo íon triiodeto

RESUMO O desempenho do polímero condutor, dopado pelo íon triiodeto, na detecção eletroquímica do ácido ascórbico foi avaliado matematicamente. O modelo matemático, correspondente ao sistema, foi desenvolvido e analisado mediante a teoria de estabilidade linear e de bifurcações. Verificou-se que o polímero condutor pode servir de excelente modificador de elétrodo para a detecção do ácido ascórbico, sendo o triiodeto a substância ativa, e o polímero condutor o mediador. O estado estacionário mantém-se estável facilmente, o que corresponde à vasta zona da linearidade da dependência entre a concentração do fármaco e o parâmetro eletroquímico. A possibilidade das instabilidades oscilatória e monotônica também foi verificada.

SUMMARY The function of the conducting polymer, doped by triiodide ion in the electrochemical determination of the ascorbic acid has been mathematically evaluated. The mathematical model, correspondent to the system, was developed and analyzed by linear stability theory and bifurcation analysis. It was confirmed that the conducting polymer might be an excellent electrode modifier for ascorbic acid determination. The triiodide ion acts as the active substance, and the conducting polymer, as a mediator. The stable steady-state is easy maintain, which is correspondent to the vast zone of the linear dependence between the drug concentration and electrochemical parameter The possibility of oscillatory and monotonic instabilities has also been verified.

The theoretical analysis of the possibility of the electrochemical determination of saccharin, assisted by vanadium (III) oxyhydroxide

RESUMEN Mediante el análisis mecanístico teórico, ha sido evaluada la posibilidad del empleo del oxihidróxido de vanadio como modificador de electrodo para la detección electroquímica de sacarina. El proceso electroanalítico se realiza a través de un proceso catódico. El modelo matemático correspondiente ha sido analizado mediante la teoría de estabilidad lineal y análisis de bifurcaciones. El análisis del modelo ha mostrado que el oxihidróxido de vanadio puede ser un modificador eficiente para la detección electroquímica de la sacarina en las condiciones del pH suficientemente ácido para mover el proceso, pero insuficiente para disolver el oxihidróxido. Las causas de los comportamientos oscilatorio y monotónico también fueron estipuladas.

SUMMARY By means of the theoretical mechanistic analysis, the possibility of the use of vanadium oxyhydroxide as electrode modifier for saccharin electrochemical determination has been evaluated. The electroanalytical process is realizing by a cathodic route. The correspondent mathematical model has been analyzed by means of the linear stability theory and bifurcation analysis. The analysis of the model has shown that the vanadium oxyhydroxide is an efficient electrode modifier for saccharin electrochemical detection in pH sufficiently low to maintain the process, but insufficiently acidic to dissolve the oxyhydroxide. The causes for the oscillatory and monotonic instabilities have also been derived.

Extraction of glycoalkaloids of native potato (Solanum phureja) ratona morada variety with pressurized liquids

RESUMEN La cáscara de papa es un residuo originado por su procesamiento agroindustrial, que genera un gran impacto ambiental debido a su inadecuado manejo o eliminación. No obstante, la cáscara de papa es una buena fuente de ingredientes funcionales como los glicoalcaloides (GA). Este estudio investigó la extracción de dos GA (α-solanina y α-chaconina) de cáscara de papa nativa (Solanum phureja) variedad ratona morada del departamento de Nariño-Colombia, utilizando la tecnología de extracción con líquidos presurizados (ELP), mediante un diseño experimental central compuesto, con el fin de determinar el efecto de la presión (P) y la temperatura (T), sobre el rendimiento y la composición de GA. Los extractos se analizaron por cromatografía líquida HPLC. Los resultados obtenidos permitieron establecer que la temperatura ejerció un efecto significativo (p <0,05) sobre el rendimiento, α-solanina y α-chaconina. El rendimiento óptimo fue de 5,62 % p/p. Los GA, α-solanina y α-chaconina, aumentaron su concentración al disminuir la temperatura. La extracción con líquidos presu-rizados promete ser una buena alternativa al uso de solventes orgánicos para obtener compuestos bioactivos de cáscara de papa.

SUMMARY Potato peel is a waste originated by its agro-industrial processing, generating an environmental impact due to its inadequate handling or elimination. However, potato peel is a good source of functional ingredients such as glycoalkaloids (GA). This study investigated the extraction of two GA (α-solanine and α-chaconine) from native potato rind (Solanum phureja) ratona morada variety from the department of Nariño-Colombia, using the technology of extraction with pressurized liquids (PLE), through a experimental central composite design, in order to determine the effect of pressure (P) and temperature (T), on the performance and composition of GA. The extracts were analyzed by liquid chromatography HPLC. The results obtained allowed us to establish that the temperature exerted a significant effect (p <0.05) on the yield, α-solanine and α-chaconine. For the yield an optimum value of 5.62 % w/w was reached. α-solanine and α-chaconine increased their concentration as the temperature decreased. The extraction with pressurized liquids promises to be a good alternative in the use of organic solvents to obtain bioactive compounds of potato husk.