ABSTRACT
Se describe un caso de influenza A H1N1 en una embarazada de 23 años con embarazo de 36 semanas quien consultó por presentar tos productiva, fiebre, mialgia y náuseas de 5 días de evolución. La radiografía de tórax reveló infiltrados en la parte inferior de ambos campos pulmonares compatibles con neumonía basal bilateral, iniciándose el tratamiento con antibióticos y antivirales. Posteriormente, se obtienen los resultados de virología que confirman la infección por virus de influenza A H1N1. Al quinto día la paciente presenta contracciones uterinas, produciéndose parto vaginal sin complicaciones, obteniéndose un recién nacido vivo femenino. Las condiciones clínicas de la paciente mejoraron lentamente y fue dada de alta al sexto día del puerperio
We describe a case of influenza A H1N1 in a 23-year-old woman at 23 weeks of pregnancy who presented with a 5-day history of productive cough, fever, myalgia, and nausea. Chest radiography showed infiltrates in the lower lobes of both pulmonary fields compatible with bilateral basal pneumonia. Treatment was started with antibiotic and antiviral therapy. Virology results subsequently confirmed influenza A H1N1 virus infection. On the fifth day, the patient developed uterine contractions and delivered a live female neonate through the vaginal route without complications. The patient's clinical status slowly improved and she was discharged on the sixth day of the puerperium
Subject(s)
Female , Humans , Pregnancy , Young Adult , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza, Human/complications , Antiviral Agents/therapeutic use , Pregnancy Complications, Infectious/diagnosis , Pregnancy OutcomeABSTRACT
Plasmodium parasites degrade hemoglobin producing reactive oxygen species as toxic byproducts which are detoxified by a series of antioxidant mechanisms. Quinoline compounds have demonstrated activity against hemoglobin degradation with 5,8-dimethylthieno[2,3-b]quinoline-2-carboxylic acid (TQCA) representing a recent compound inhibiting this process. Thus, this study was undertaken to determine the ability of TQCA to modify the oxidative status in Plasmodium berghei-infected erythrocytes. After hemolysis, activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and dehydrogenase enzymes as well as lipid peroxidation were investigated by spectrophotometry. Saturated and unsaturated fatty acids were determined by gas-liquid chromatography and the in vivo effects of TQCA were confirmed by a malaria murine model (Rane test). The activity of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) in infected cells was diminished by this compound compared to control infection in 75.1 ± 3.5% and 26.5 ± 0.3%, respectively, while that of GPx and GR was also lowered (p <0.05). As an adaptive response we appreciated a 2.3-fold increase of SOD activity compared to control infection. Lipid peroxidation and the saturated/unsaturated fatty acids ratio were also decreased by this quinoline derivate in 49.2 ± 1.32% and 37 ± 0.06%, respectively, protecting the cells from hemolysis caused by the infection. The in vitro results were in concordance with the potential in vivo activity of this compound in an established malaria murine model in which TQCA showed significant decrease in the parasitemia levels and increased the mean survival days of infected mice. In conclusion, the antioxidant defense represents a biochemical target for TQCA actions as a potent antimalarial whose effects were also confirmed in vivo.
Subject(s)
Antimalarials/pharmacology , Erythrocytes/parasitology , Plasmodium berghei/physiology , Quinolines/pharmacology , Thiophenes/pharmacology , Animals , Antimalarials/chemical synthesis , Antioxidants/metabolism , Catalase/metabolism , Erythrocyte Membrane/drug effects , Erythrocytes/drug effects , Erythrocytes/metabolism , Glucosephosphate Dehydrogenase/metabolism , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Lipid Peroxidation , Male , Membrane Lipids/blood , Mice , Mice, Inbred BALB C , Phosphogluconate Dehydrogenase/metabolism , Plasmodium berghei/drug effects , Quinolines/chemical synthesis , Superoxide Dismutase/metabolism , Thiophenes/chemical synthesisABSTRACT
Objetivo Comparar las concentraciones de interleucina-16 en pacientes con preeclampsia y gestantes normotensas sanas. Método Se seleccionó un total de 100 pacientes. Se incluyeron 50 pacientes con preeclampsia como grupo de estudio (grupo A) y un grupo de control seleccionado por tener una edad y un índice de masa corporal similares al grupo de estudio que consistió en 50 gestantes normotensas sanas (grupo B). Las muestras de sangre se recolectaron en todas las pacientes antes del parto e inmediatamente después del diagnóstico en el grupo B para determinar las concentraciones de interleucina-16.ResultadosSe encontraron diferencias estadísticamente significativas en las concentraciones de interleucina-16 entre las pacientes del grupo de estudio (grupo A: 211,9 ± 78,7 pg/ml) y las pacientes del grupo de control (grupo B: 83,6 ± 9,9 pg/ml; p < 0,05). Se observó una correlación fuerte, positiva y significativa con los valores de presión arterial sistólica (r = 0,282; p < 0,05) y con los valores de presión arterial diastólica (r = 0,320; p < 0,05). Un valor de corte de 180 pg/ml presentó un valor por debajo de la curva de 0,95, una sensibilidad del 94,0%, especificidad del 70,0%, valor predictivo positivo del 75,8% y valor predictivo negativo del 92,1%, con una exactitud diagnóstica del 75,0%.ConclusionesLas pacientes con preeclampsia presentaron concentraciones significativamente más altas de interleucina-16 al compararlo con gestantes normotensas sanas (AU)
Objective To compare interleukin-16 concentrations in patients with preeclampsia and healthy normotensive pregnant women. Method A total of 100 patients were selected. Fifty patients with preeclampsia were selected as the study group (group A) and 50 healthy normotensive pregnant women with the same age and body mass index as the study group were selected as controls (group B). Blood samples were extracted from all patients before labor and immediately after diagnosis in group B to determine interleukin-16 concentrations. Results There was statistically significant difference in interleukin-16 concentrations between group A (211.9 ± 78.7 pg/ml) and group B (83.6 ± 9.9 pg/ml; p < 0.05). There was a strong, positive and significant correlation with systolic blood pressure values (r = 0.282; p < 0.05) and with diastolic blood pressure values (r = 0.320; p < 0.05). A cutoff value of 180 pg/ml had an area under the curve of 0.95, sensitivity of 94.0%, specificity of 70.0%, a positive predictive value of 75.8% and a negative predictive value of 92.1%, with a diagnostic accuracy of 75.0%.ConclusionsInterleukin-16 concentrations were significantly higher in patients with preeclampsia than in healthy normotensive pregnant women (AU)
Subject(s)
Humans , Female , Pregnancy , Interleukin-16/analysis , Pre-Eclampsia/physiopathology , Pregnancy Complications/diagnosis , Biomarkers/analysisABSTRACT
Objetivo Comparar las concentraciones de interleucina-15 en pacientes con preeclampsia y embarazadas normotensas sanas. Método Se seleccionó un total de 100 pacientes. Se incluyeron 50 pacientes preeclámpticas como los casos (grupo A) y un grupo control seleccionado por tener una edad y un índice de masa corporal similares al grupo de estudio que consistió en 50 embarazadas normotensas sanas (grupo B). Las muestras de sangre se recolectaron en todas las pacientes antes del parto e inmediatamente después del diagnóstico en el grupo B para determinar las concentraciones de interleucina-15.ResultadosNo se encontraron diferencias significativas con relación a la edad materna, edad gestacional e índice de masa corporal al momento de la toma de la muestra (p=ns). Se encontraron diferencias estadísticamente significativa en las concentraciones de interleucina-15 entre las pacientes en el grupo de estudio (grupo A; 3,21±0,79pg/ml) y las pacientes del grupo control (grupo B; 2,26±0,24pg/ml; p<0,05). Se observó una correlación moderada, positiva y significativa con los valores de presión arterial sistólica (r=0,584; p<0,05) y con los valores de presión arterial diastólica (r=0,589; p<0,05).Conclusiones Las preeclámpticas presentaron concentraciones significativamente más altas de interleucina-15 al compararlo con embarazadas normotensas sanas (AU)
Objective To compare interleukin-15 concentrations in preeclamptic patients and healthy normotensive pregnant women. Method A total of 100 patients were selected. Fifty preeclamptic patients were selected as cases (group A) and 50 normotensive pregnant women with a similar age and body mass index to the study group were selected as controls (group B). Blood samples were collected before labor in all patients and immediately after diagnosis in group B to determine interleukin-15 concentrations. Results There were no significant differences in maternal age, gestational age or body mass index at sample extraction (p=ns). Interleukin-15 concentrations were significantly higher in patients in the study group (group A; 3.21±0.79pg/ml) than in those in the control group (group B; 2.26±0.24pg/ml; p<0.05). There was a moderate, positive and significant correlation with systolic blood pressure values (r=0.584; p<0.05) and diastolic blood pressure values (r=0.589; p<0.05).ConclusionsInterleukin-15 concentrations were significantly higher in preeclamptic patients than in healthy normotensive pregnant women (AU)
Subject(s)
Humans , Female , Pregnancy , Interleukin-15/analysis , Pre-Eclampsia/physiopathology , Biomarkers/analysis , Pregnancy Complications/physiopathologyABSTRACT
La patogénesis de la disección espontánea aguda de las arterias coronarias relacionada con el embarazo aun no ha sido completamente comprendida. Ochenta por ciento ocurren en mujeres. Un tercio de los casos se observan en el embarazo o en el posparto. La mayoría de los casos han ocurrido en el puerperio. Se presenta un caso de paciente de 36 años, 2 gestas 1 para, que cuatro horas después del parto refirió dolor torácico que se irradia a la espalda y brazo izquierdo. La coronariografía demostró un sistema coronario izquierdo normal y una extensa disección de la arteria coronaria derecha. La paciente fue tratada farmacológicamente y posteriormente sometida a una cirugía de bypass del vaso coronario afectado (AU)
The pathogenesis of pregnancy-related spontaneous coronary artery dissection(SCAD) has not yet been fully elucidated. Eighty percent of SCAD cases occur in women. One third of cases are observed during pregnancy or the postpartum. Most cases occur in the puerperium. We present the case of a 26-year-old woman (gesta 2, para 1), who reported chest pain radiating to her back and left arm 4 hours after delivery. Coronary angiography showed anormal left coronary system and extensive dissection of the right coronary artery. The patient was treated pharmacologically and later underwent surgical bypass of the affected coronary vessel (AU)
Subject(s)
Humans , Female , Adult , Coronary Aneurysm/diagnosis , Coronary Artery Bypass, Off-Pump , Postpartum Period , Risk Factors , Arteriovenous Shunt, Surgical , Chest Pain/etiologyABSTRACT
El sistema dopaminergico central está implicado en las diversas etiologías que involucran a patologías neuropsiquiátricas, tales como la enfermedad de Parkinson, la depresión y la esquizofrenia. Son numerosas las drogas dopaminérgicas utilizadas en el tratamiento de esas dolencias, sin embargo estas terapias causan serios efectos adversos. En este contexto, la génesis de nuevos y más eficientes agentes dopaminergicos, representa un vasto campo de investigación. En el presente trabajo se sintetizó el compuesto 3, concebido como un ligando dopaminérgico, y se evaluó el perfil de su acción dopaminérgica mediante administración central del compuesto y la determinanción de parámetros conductuales como el comportameinto estereotipado (roer) y la medición de la respuesta renal en ratas. Los resultados de la evaluación farmacológica muestran que el compuesto 3 bloquea significativamente la estereotipia inducida por apomorfina, e inhibe la diuresis y natriuresis inducida por la administración central de dopamina. Estos hallazgos sugieren que el compuesto 3 se comporta como un antagonista dopaminérgico, frente a la respuesta tanto conductuales como renales
Subject(s)
Animals , Rats , Depression/pathology , Dopamine , Parkinson Disease , Receptors, Dopamine/therapeutic use , Schizophrenia , Pharmacology , Therapeutics , VenezuelaABSTRACT
The synthetic chalcone derivative 1-(2,4-dichlorophenyl)-3-(3-(6,7-dimethoxy-2-chloroquinolinyl))-2-propen-1-one (ClDQ) was evaluated for its anti-inflammatory, analgesic and immunomodulatory efficacy in-vitro and in-vivo. ClDQ concentration-dependently inhibited the production of nitric oxide (NO) (IC50 4.3 microM) and prostaglandin E(2) (PGE(2)) (IC50 1.8 microM) in RAW 264.7 macrophages stimulated with lipopolysaccharide. Human mononuclear cell proliferation was significantly inhibited by 10 microM ClDQ. Oral administration of ClDQ (10-30 mg kg(-1)) in the 24-h zymosan-stimulated mouse air-pouch model produced a dose-dependent reduction of cell migration as well as NO and PGE(2) levels in exudates. ClDQ (20 mg kg(-1), p.o.) inhibited ear swelling and leucocyte infiltration in the delayed-type hypersensitivity response to 2,4-dinitrofluorobenzene in mice. In the rat adjuvant-arthritis model, this compound reduced joint inflammation as well as PGE(2) and cytokine levels. In addition, ClDQ displayed analgesic effects in the phenylbenzoquinone-induced abdominal constriction model in mice and in the late phase of the nociceptive response to formalin. Our findings indicated the potential interest of ClDQ in the modulation of some immune and inflammatory conditions.
Subject(s)
Inflammation/prevention & control , Pyridazines/chemical synthesis , Abdominal Injuries/chemically induced , Abdominal Injuries/prevention & control , Administration, Oral , Animals , Arthritis, Experimental/chemically induced , Arthritis, Experimental/immunology , Blood Platelets/drug effects , Blood Platelets/enzymology , Cell Line , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Dinitrofluorobenzene , Dinoprostone/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Hypersensitivity/immunology , Drug Hypersensitivity/prevention & control , Female , Formaldehyde , Group II Phospholipases A2 , Group IV Phospholipases A2 , Humans , Inflammation/chemically induced , Lipopolysaccharides/pharmacology , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Mice , Microsomes/drug effects , Microsomes/enzymology , Nitrites/metabolism , Pain/chemically induced , Pain/prevention & control , Pain Measurement/methods , Phospholipases A/antagonists & inhibitors , Phospholipases A/metabolism , Pyridazines/pharmacology , Rats , Rats, Inbred Lew , Thromboxane B2/metabolism , ZymosanABSTRACT
OBJECTIVE AND DESIGN: The synthetic chalcone derivative 1-(2,3,4-trimethoxyphenyl)-3-(3-(2-chloroquinolinyl))-2-propen-1-one (TQ) was evaluated for its immunomodulatory and anti-inflammatory efficacy in vitro and in vivo. MATERIAL AND SUBJECTS: Human neutrophils and lymphocytes from healthy volunteers and RAW 264.7 murine macrophages. Swiss mice and Lewis rats were randomly divided into groups of six animals. TREATMENT: TQ was orally administered in all in vivo assays (10-30 mg/kg). METHODS: Elastase, superoxide and LTB(4) release were assayed in human neutrophils, NO/PGE(2) production and NF-kappaB activation in RAW 264.7, and (3)H thymidine incorporation in human lymphocytes. Zymosan-stimulated air pouches, DNFB-DTH, PBQ-induced writhings and formalin-induced pain were assayed in mice. Adjuvant-induced arthritis was tested in rats. Dunnett's t-test was employed for statistical analysis. RESULTS: Human T-cell proliferation, neutrophil functions and NO/PGE(2) production in murine macrophages were inhibited by TQ (IC(50) in the microM range), which showed anti-inflammatory, immunomodulatory and analgesic effects. CONCLUSIONS: Our findings indicate the potential interest of TQ in the modulation of some immune and inflammatory responses probably by NF-kappaB inhibition.
Subject(s)
Adjuvants, Immunologic/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Chalcone/pharmacology , Quinolines/pharmacology , Animals , Arthritis, Experimental/drug therapy , Blotting, Western , Cell Division , Chalcone/analogs & derivatives , Chalcones , Cyclooxygenase 1 , Cyclooxygenase 2 , Dinoprostone/biosynthesis , Edema/chemically induced , Edema/prevention & control , Electrophoretic Mobility Shift Assay , Humans , Hypersensitivity, Delayed/drug therapy , In Vitro Techniques , Indicators and Reagents , Isoenzymes/biosynthesis , Leukocyte Elastase/metabolism , Leukotriene B4/biosynthesis , Luminescent Measurements , Lymphocyte Activation/drug effects , Macrophage Activation/drug effects , Membrane Proteins , Mice , Neutrophil Activation/drug effects , Nitric Oxide Synthase/biosynthesis , Nitric Oxide Synthase Type II , Nitrites/metabolism , Pain/chemically induced , Pain/prevention & control , Pain Measurement/drug effects , Phospholipases A/biosynthesis , Prostaglandin-Endoperoxide Synthases/biosynthesisABSTRACT
Quinolinyl chalcones were synthesized and evaluated for their inhibition of the Plasmodium falciparum cystein protease falcipain and their activity against cultured P. falciparum parasites. They were also tested for in vivo efficacy in a rodent P. berghei model. Their activity against falcipain and as antimalarials was moderate, but antimalarial activity was probably not due to the inhibition of falcipain and may follow a different mechanism. 1-(2,4-Dichlorophenyl)-3-[3-(2-chloro-6,7-dimethoxiquinolinyl)]-2-propen-1-one 3j was the most promising compound among those here reported (IC50 19.0 microM).
Subject(s)
Antimalarials/chemical synthesis , Antimalarials/pharmacology , Chalcone/analogs & derivatives , Chalcone/pharmacology , Quinolones/pharmacology , Animals , Antimalarials/chemistry , Antimalarials/therapeutic use , Chalcone/chemical synthesis , Chalcone/therapeutic use , Drug Design , Drug Evaluation, Preclinical , Endopeptidases/metabolism , Gas Chromatography-Mass Spectrometry , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Malaria/drug therapy , Male , Mice , Mice, Inbred BALB C , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Quinolones/chemical synthesis , Quinolones/chemistry , Quinolones/therapeutic use , Structure-Activity RelationshipABSTRACT
Here we report the synthesis, in vitro antifungal evaluation and SAR study of 41 chalcones and analogues. In addition, all active structures were tested for their capacity of inhibiting Saccharomyces cerevisiae beta(1,3)-glucan synthase and chitin synthase, enzymes that catalyze the synthesis of the major polymers of the fungal cell wall.
Subject(s)
Antifungal Agents/pharmacology , Cell Wall/drug effects , Chalcone/pharmacology , Saccharomyces cerevisiae/drug effects , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Cell Wall/metabolism , Chalcone/chemical synthesis , Chalcone/chemistry , Evaluation Studies as Topic , Microbial Sensitivity Tests , Molecular Conformation , Polymers , Saccharomyces cerevisiae/metabolism , Structure-Activity RelationshipABSTRACT
Reactive oxygen and nitrogen species contribute to the pathophysiology of inflammatory conditions. We have studied the effects of a novel superoxide scavenger, 4-dimethylamino-3', 4'-dimethoxychalcone (CH11) in macrophages and in vivo. CH11 has been shown to inhibit the chemiluminescence induced by zymosan in mouse peritoneal macrophages and the cytotoxic effects of superoxide. In the same cells, the modulation by superoxide of nitric oxide (NO) production in response to zymosan was investigated. CH11 was more effective than the membrane-permeable scavenger Tiron for inhibition of inducible nitric oxide synthase (iNOS) protein expression and nitrite production. We have shown that CH11 inhibited chemiluminescence in vivo, as well as cell migration, and eicosanoid and tumor necrosis factor-alpha (TNF-alpha) levels in the mouse air pouch injected with zymosan. This chalcone derivative also exerted anti-inflammatory effects in the carrageenan paw oedema.
Subject(s)
Chalcone/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Inflammation/drug therapy , Nitric Oxide Synthase/genetics , 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/pharmacology , Animals , Anti-Inflammatory Agents/therapeutic use , Carrageenan , Chalcone/analogs & derivatives , Chalcone/therapeutic use , Chalcones , Edema/chemically induced , Edema/drug therapy , Enzyme Inhibitors/pharmacology , Female , Free Radical Scavengers , Luminescent Measurements , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/physiology , Mice , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type II , Oxidative Stress , Respiratory Burst/drug effects , Superoxides/pharmacology , Zymosan/pharmacologyABSTRACT
(+/-)-1-Amino-6,7,8,8a-tetrahydroacenaphthene was synthesized and evaluated as a novel drug acting on the dopaminergic system. It was shown that the new compound displays activity as MAO inhibitor.
Subject(s)
Acenaphthenes/chemical synthesis , Cerebral Cortex/enzymology , Liver/enzymology , Monoamine Oxidase Inhibitors/chemical synthesis , Acenaphthenes/pharmacology , Animals , Cerebral Cortex/drug effects , Dopamine/physiology , Liver/drug effects , Male , Monoamine Oxidase Inhibitors/pharmacology , Rats , Rats, Sprague-Dawley , Spectrophotometry, Infrared , StereoisomerismABSTRACT
Compound 2 considered as a rigid non-hydroxylated 2-amino tetralin was synthesized and biologically evaluated. Central administration of compound 2 (50 microg or 100 microg/10 microl) induced a reduction in urinary sodium and potassium excretion at 3 and 6 h of urine collection. We speculate that compound 2 may be acting as a dopamine receptor antagonist.
Subject(s)
Amines/pharmacology , Dopamine Antagonists/pharmacology , Dopamine D2 Receptor Antagonists , Heterocyclic Compounds/pharmacology , Phenalenes , Polycyclic Compounds/pharmacology , Receptors, Dopamine D1/antagonists & inhibitors , Amines/chemical synthesis , Amines/chemistry , Animals , Diuresis/drug effects , Dopamine Antagonists/chemical synthesis , Dopamine Antagonists/chemistry , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Male , Molecular Structure , Natriuresis/drug effects , Polycyclic Compounds/chemical synthesis , Polycyclic Compounds/chemistry , Potassium/urine , Rats , Rats, Sprague-Dawley , Sodium/urineABSTRACT
In a previous work, we tested a series of chalcone derivatives as possible anti-inflammatory compounds. We now investigate the effects of three of those compounds, CHI, CH8 and CH12, on nitric oxide and prostanoid generation in mouse peritoneal macrophages stimulated with lipopolysaccharide and in the mouse air pouch injected with zymosan, where they showed a dose-dependent inhibition with inhibitory concentration 50% values in the microM range. This effect was not the consequence of a direct inhibitory action on enzyme activities. Our results demonstrated that chalcone derivatives inhibited de novo inducible nitric oxide synthase and cyclooxygenase-2 synthesis, being a novel therapeutic approach for inflammatory diseases.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Chalcone/analogs & derivatives , Isoenzymes/biosynthesis , Macrophages, Peritoneal/enzymology , Nitric Oxide Synthase/biosynthesis , Prostaglandin-Endoperoxide Synthases/biosynthesis , Animals , Cyclooxygenase 2 , Dinoprostone/biosynthesis , Dose-Response Relationship, Drug , Enzyme Induction/drug effects , Female , Lipopolysaccharides/pharmacology , Mice , Nitric Oxide Synthase Type II , Nitrites/metabolism , Zymosan/pharmacologyABSTRACT
Chalcones and their derivatives were synthesized and evaluated for their anti-inflammatory activity. In vitro, chalcones 2, 4, 8, 10 and 13 inhibited degranulation and 5-lipoxygenase in human neutrophils, whereas 11 behaved as scavenger of superoxide. Only four compounds (4-7) inhibited cyclo-oxygenase-2 activity. The majority of these samples showed anti-inflammatory effects in the mouse air pouch model.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Chalcone/analogs & derivatives , Chalcone/chemical synthesis , Propiophenones/chemical synthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arachidonate 5-Lipoxygenase/blood , Chalcone/chemistry , Chalcone/pharmacology , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/chemistry , Cyclooxygenase Inhibitors/pharmacology , Drug Design , Humans , Isoenzymes/blood , Leukotriene B4/blood , Lipoxygenase Inhibitors/chemical synthesis , Lipoxygenase Inhibitors/chemistry , Lipoxygenase Inhibitors/pharmacology , Membrane Proteins , Mice , Molecular Structure , Neutrophils/drug effects , Neutrophils/physiology , Propiophenones/chemistry , Propiophenones/pharmacology , Prostaglandin-Endoperoxide Synthases/blood , Structure-Activity RelationshipABSTRACT
Acridinediones have previously been shown to have potent antimalarial activity. A series of sulfur isosteres of acridinediones have been synthesized and evaluated for their inhibition of the Plasmodium falciparum cysteine protease falcipain and for their antimalarial activity. A number of these phenothiazines inhibited falcipain and demonstrated activity against cultured P. falciparum parasites at low micromolar concentrations. We propose that the compounds exerted their antimalarial effects by two mechanisms, one of which involves the inhibition of falcipain and a consequent block in parasite degradation of hemoglobin. These compounds and related phenothiazines are worthy of further study as potential antimalarial agents.
Subject(s)
Antimalarials/chemical synthesis , Cysteine Endopeptidases/metabolism , Cysteine Proteinase Inhibitors/chemical synthesis , Phenothiazines/chemistry , Plasmodium falciparum/enzymology , Animals , Antimalarials/pharmacology , Cells, Cultured , Cysteine Proteinase Inhibitors/pharmacology , Phenothiazines/pharmacology , Plasmodium falciparum/drug effectsABSTRACT
Amino substitution of rigid forms of dopamine 4,5-dihydroxy-2-aminoindan and 5,6-dihydroxy-2-aminoindan with aralkyl functionalities were carried out to investigate the role of such structural modifications upon cardiac inotropic-chronotropic activity. Compounds synthesized demonstrated a modest inotropic selectivity, while one of them, described as 5,6-dihydroxy-N-[2-(4-hydroxyphenyl)-1-methylethyl]-2-aminoindan hydrobromide 17, showed a marked inotropic action on isolated heart tissue.
Subject(s)
Cardiotonic Agents/chemical synthesis , Heart Rate/drug effects , Indans/chemical synthesis , Myocardial Contraction/drug effects , Animals , Cardiotonic Agents/pharmacology , Guinea Pigs , In Vitro Techniques , Indans/pharmacology , MaleABSTRACT
Pyridopyrimidone derivatives 4a-d and 5a- were synthesized as potential antimalarial agents on the basis of the pharmacological properties of existing quinolone analogues such as ciprofloxacine IC50 39.8 microM. Meanwhile among these new compounds, only the 3-amino-7-methyl-1(H)pyrazolo[3,4-b]-pyrido [1,2: 1'2']pyrimido-4-ona 4b, produces significant antimalarial activity IC50 0.42 microM against P. falciparum in vitro. The remaining compounds were effective as antimalarial agents leading from IC50 1.0 microM to IC50 4.47 microM.
Subject(s)
Antimalarials/chemical synthesis , Plasmodium falciparum/drug effects , Pyrimidinones/chemical synthesis , Animals , Antimalarials/pharmacology , Chemical Phenomena , Chemistry, Physical , Erythrocytes/drug effects , Erythrocytes/parasitology , Humans , In Vitro Techniques , Magnetic Resonance Spectroscopy , Pyrimidinones/pharmacologyABSTRACT
Quinolones 7a-i and 8a-i were synthesized and tested in vitro as antimalarial against Plasmodium falciparum in chloroquine resistant strain. The above compounds were inactive at concentrations of 1.0 x 10(-4) M except the quinolone 3-amino-9-(2,4-dichlorophenyl)-1H-pyrazolo[3,4-b]-4-quinolone 7h which showed IC50 of 5.06 microM given the most interesting results.