RESUMEN
While Health authorities in Panama strive to increase generic drug use to contain the rising costs of medicines, there is still hesitation to embrace generic drugs. Thus, regulators and drug companies need to ensure the quality, safety and efficacy of generic drugs. One prevailing concern is the absence of control over lot-to-lot changes, which may impact consistent therapeutic performance. The objective of this work was to determine whether near-infrared spectroscopy (NIR) could detect product changes. Calibration models were built using reference (standard) tablets of two products: Virax® (200 mg acyclovir) and Amlopin® (5 mg amlodipine). Then, to assess the sensitivity of NIR to product changes we compared reference versus deliberately-modified formulations of these products. Comparisons were made using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) of NIR spectra. Several modified lots were different from reference lots, and 3D score plots showed greater discrimination by PLS-DA than PCA. The Kth nearest neighbor scores (KNN) of the modified batches were used to classify formulations as identical or not identical versus the reference. In addition, the differences detected by NIR were correlated with different in vitro dissolution and/or permeation in the in vitro dissolution absorption system 2 (IDAS2): NIR and IDAS2 yielded the same rank-order of difference for the modified lots tested. This study suggests that NIR and IDAS2 can help detect lots of generic drugs that differ from the reference lots. This strategy may help regulatory agencies in developing countries to safeguard patients against lot-to-lot changes in generic products.
Asunto(s)
Medicamentos Genéricos , Espectroscopía Infrarroja Corta/métodos , Química Farmacéutica/métodos , Análisis de Componente PrincipalRESUMEN
Compound databases of natural products play a crucial role in drug discovery and development projects and have implications in other areas, such as food chemical research, ecology and metabolomics. Recently, we put together the first version of the Latin American Natural Product database (LANaPDB) as a collective effort of researchers from six countries to ensemble a public and representative library of natural products in a geographical region with a large biodiversity. The present work aims to conduct a comparative and extensive profiling of the natural product-likeness of an updated version of LANaPDB and the individual ten compound databases that form part of LANaPDB. The natural product-likeness profile of the Latin American compound databases is contrasted with the profile of other major natural product databases in the public domain and a set of small-molecule drugs approved for clinical use. As part of the extensive characterization, we employed several chemoinformatics metrics of natural product likeness. The results of this study will capture the attention of the global community engaged in natural product databases, not only in Latin America but across the world.
Asunto(s)
Productos Biológicos , Productos Biológicos/química , Productos Biológicos/farmacología , América Latina , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/química , Descubrimiento de Drogas , Quimioinformática , Bases de Datos de Compuestos QuímicosRESUMEN
Increased activation and proliferation of T lymphocytes plays an essential role in the development of chronic inflammation and autoimmune diseases. Currently used immunosuppressive drugs often do not provide long-lasting relief of symptoms and show a gradual loss of efficacy over time, and are accompanied by various side effects. Therefore, novel immunosuppressive lead substances are needed. For this purpose, an in-house library consisting of 600 extracts of plants from Panama was screened for inhibition of human T lymphocyte proliferation. As one of the hits, an ethyl acetate extract from the aerial parts of Hyptis brachiata (Lamiaceae) exhibited strong inhibitory effects. Subsequent investigation resulted in the isolation of seven aryltetralin lignans, five arylnaphthalene lignans, two flavonoids, three triterpenes, and cinnamyl cinnamate. Aryltetralin lignans inhibited T lymphocyte proliferation in a concentration-dependent manner without induction of apoptosis. No relevant inhibition was observed for the arylnaphthalene lignans, flavonoids, and triterpenes. Additional cell cycle arrest investigations revealed that isolated aryltetralin lignans potently inhibited cell division in G2/M phase similarly to podophyllotoxin. Multifluorescence panel analyses of the extract also showed weak suppressive effects on the production of IL-2 and TNF-α. Therefore, preparations made out of H. brachiata could be further explored as an interesting herbal alternative in the treatment of autoimmune diseases.
Asunto(s)
Hyptis , Lamiaceae , Lignanos , Humanos , Lignanos/farmacología , Podofilotoxina/farmacología , Proliferación CelularRESUMEN
BACKGROUND: The microplate benchtop brine shrimp test (BST) has been widely used for screening and bio-guided isolation of many active compounds, including natural products. Although the interpretation given to the results appears dissimilar, our findings suggest a correlation between positive results with a specific mechanism of action. OBJECTIVE: This study aimed to evaluate drugs belonging to fifteen pharmacological categories having diverse mechanisms of action and carry out a bibliometric analysis of over 700 citations related to microwell BST. METHODS: Test compounds were evaluated in a serial dilution on the microwell BST using healthy nauplii of Artemia salina and after 24 hrs of exposition, the number of alive and dead nauplii was determined, and the LC50 was estimated. A metric study regarding the citations of the BST miniaturized method, sorted by type of documents cited, contributing country, and interpretation of results was conducted on 706 selected citations found in Google Scholar. RESULTS: Out of 206 drugs tested belonging to fifteen pharmacological categories, twenty-six showed LC50 values <100 µM, most of them belonging to the category of antineoplastic drugs; compounds with different therapeutical uses were found to be cytotoxic as well. A bibliometric analysis showed 706 documents citing the miniaturized BST; 78% of them belonged to academic laboratories from developing countries located on all continents, 63% interpreted their results as cytotoxic activity and 35% indicated general toxicity assessment. CONCLUSION: BST is a simple, affordable, benchtop assay, capable of detecting cytotoxic drugs with specific mechanisms of action, such as protein synthesis inhibition, antimitotic, DNA binding, topoisomerase I inhibitors, and caspases cascade interfering drugs. The microwell BST is a technique that is used worldwide for the bio-guided isolation of cytotoxic compounds from different sources.
RESUMEN
The number of databases of natural products (NPs) has increased substantially. Latin America is extraordinarily rich in biodiversity, enabling the identification of novel NPs, which has encouraged both the development of databases and the implementation of those that are being created or are under development. In a collective effort from several Latin American countries, herein we introduce the first version of the Latin American Natural Products Database (LANaPDB), a public compound collection that gathers the chemical information of NPs contained in diverse databases from this geographical region. The current version of LANaPDB unifies the information from six countries and contains 12,959 chemical structures. The structural classification showed that the most abundant compounds are the terpenoids (63.2%), phenylpropanoids (18%) and alkaloids (11.8%). From the analysis of the distribution of properties of pharmaceutical interest, it was observed that many LANaPDB compounds satisfy some drug-like rules of thumb for physicochemical properties. The concept of the chemical multiverse was employed to generate multiple chemical spaces from two different fingerprints and two dimensionality reduction techniques. Comparing LANaPDB with FDA-approved drugs and the major open-access repository of NPs, COCONUT, it was concluded that the chemical space covered by LANaPDB completely overlaps with COCONUT and, in some regions, with FDA-approved drugs. LANaPDB will be updated, adding more compounds from each database, plus the addition of databases from other Latin American countries.
RESUMEN
In order to explore rationally the medical potential of the plant biodiversity of the Central and South American region as a source of novel antiparasitic molecules, a multinational Organization of American States (OAS) project, which included the participation of multidisciplinary research centers from Argentina, Bolivia, Colombia, Costa Rica, Guatemala, Nicaragua and Panama, was carried out during the period 2001-2004. This project aimed at screening organic plant extracts for antitrypanosomal, antileishmanial and antimalarial activities and subsequently isolating and characterizing bioactive molecules. Plants for antiparasitic screening were selected from a database of ethnomedical uses of Latin American plants (PlanMedia) based on the amount of biological and chemical information available in the literature. We report here the evaluation of 452 extracts from 311 plant species in vitro screens against Plasmodium falciparum, Leishmania mexicana, and Trypanosoma cruzi. Out of 311 species tested, 17 plants (5.4%) showed antiparasitic activities at IC(50) values < or = 10 microg/mL. The most active plants were Acnistus arborescens (L.) Schltdl. (Solanaceae) (leaf, EtOH, IC(50): 4 microg/mL) Monochaetum myrtoideum Naudin (Melastomataceae) (leaf, MeOH, IC(50): 5 microg/mL) and Bourreria huanita (Lex.) Hemsl. (Boraginaceae) (branch, EtOH, IC(50): 6 microg/mL). These were selectively active against P. falciparum, L. mexicana and T. cruzi, respectively.
Asunto(s)
Antimaláricos/uso terapéutico , Antiparasitarios/uso terapéutico , Enfermedad de Chagas , Leishmaniasis , Malaria , Extractos Vegetales/uso terapéutico , Antimaláricos/aislamiento & purificación , Antiparasitarios/aislamiento & purificación , Enfermedad de Chagas/tratamiento farmacológico , Evaluación Preclínica de Medicamentos/métodos , Humanos , América Latina , Leishmaniasis/tratamiento farmacológico , Malaria/tratamiento farmacológico , Extractos Vegetales/aislamiento & purificación , Plantas , Distribución AleatoriaRESUMEN
A new lignan, 3,4,5'-trimethoxy-3',4'-methylenedioxy-7,9':7',9 diepoxylignan (1) (6-[4-(3,4-dimethoxy-phenyl)-tetrahydro-furo[3,4-c.]furan-1-yl]-4-methoxy-benzo[ ] dioxole) together with two known lignans, 7'-epi.-sesartemin (2) and diayangambin (3), and a known flavonoid, 5-hydroxy-7,4'-dimethoxyflavone (4), were isolated from the leaves of Piper fimbriulatum. C. DC. Their structures were assigned by a combination of one- and two-dimensional NMR techniques. 7'-epi.-Sesartemin (2) showed the highest larvicidal activity against Aedes aegypti. (LC100 17.6 µg/ml) and weak antiplasmodial (IC50 7.0 µg/ml) and antitrypanosomal (IC50 39.0 µg/ml) activities. None of the compounds was active against Leishmania mexicana..
RESUMEN
The type of interaction of 5-methyl-2,3,7,8-bis(methylenedioxy)benzo[c]phenanthridinium (sanguinarine), an alkaloid isolated from the root of Bocconia frutescens L., with the human angiotensin AT(1) receptor was evaluated in both intact cells and membrane binding of [3H](2-ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimidazoline-7-carboxylic acid) ([3H]candesartan). The results indicate that the inhibition of [3H]candesartan binding by sanguinarine is independent of cell viability, since the alkaloid inhibited at a similar extent radioligand binding on both intact Chinese hamster ovary (CHO) cells transfected with the human angiotensin AT(1) receptor (hAT(1)) and their cell membranes (K(i)=0.14 and 1.10 microM, respectively). The unsuccessful recovery of [3H]candesartan binding after washing sanguinarine off the cells suggested a nearly irreversible or slow reversible interaction. Saturation binding studies showed a substantial reduction of the B(max) without affecting the K(d). In addition, the presence of 2-n-butyl-4chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole (losartan) could not prevent sanguinarine inhibition of [3H]candesartan binding neither. The present findings indicate that sanguinarine interacts with the receptor in a slow, nearly irreversible and noncompetitive manner.
Asunto(s)
Alcaloides/farmacología , Bencimidazoles/metabolismo , Receptores de Angiotensina/metabolismo , Tetrazoles/metabolismo , Animales , Benzofenantridinas , Unión Competitiva/efectos de los fármacos , Compuestos de Bifenilo , Células CHO , Cricetinae , Relación Dosis-Respuesta a Droga , Humanos , Isoquinolinas , Receptor de Angiotensina Tipo 1 , Receptores de Angiotensina/genética , Timidina/metabolismo , Transfección , TritioRESUMEN
Ten novel neo-clerodane diterpenoids, named cornutins C-L, have been isolated from the leaves of Cornutia grandifolia var. intermedia. Their structures have been elucidated by detailed spectroscopic analysis. In addition, the in vitro antiplasmodial activity of four isolated compounds (cornutin C-F) has been evaluated, revealing only a marginal activity.
Asunto(s)
Diterpenos de Tipo Clerodano , Diterpenos/aislamiento & purificación , Verbenaceae/química , Animales , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Antimaláricos/farmacología , Diterpenos/química , Diterpenos/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Hojas de la Planta/química , Plasmodium falciparum/efectos de los fármacosRESUMEN
The phytochemical investigation of the leaves of Siparuna pauciflora yielded three novel sesquiterpenoids: the germacrane sipaucin A, the elemane sipaucin B and sipaucin C, comprising a new type of carbon skeleton. In addition, four known aporphine alkaloids-nor-boldine, boldine, laurotetanine, and N-methyl-laurotetanine-were obtained. The evaluation of the antiplasmodial activity of the isolated compounds against two strains of Plasmodium falciparum (PoW, Dd2) showed a moderate activity of nor-boldine.
Asunto(s)
Monimiaceae/química , Sesquiterpenos/aislamiento & purificación , Animales , Antiprotozoarios/química , Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/farmacología , Espectroscopía de Resonancia Magnética , Hojas de la Planta/química , Plasmodium falciparum/efectos de los fármacos , Sesquiterpenos/química , Sesquiterpenos/farmacologíaRESUMEN
Bioassay-guided fractionation of the chloroform and ethanol extracts of Tovomita longifolia leaves using cytotoxic and antimicrobial assays resulted in the isolation of four new benzophenones, (E)-3-(2-hydroxy-7-methyl-3-methyleneoct-6-enyl)-2,4,6-trihydroxybenzophenone (1), (E)-3-(6-hydroxy-3,7-dimethylocta-2,7-dienyl)-2,4,6-trihydroxybenzophenone (2), 8-benzoyl-2-(4-methylpenten-3-yl)chromane-3,5,7-triol (3), and 5-benzoyl-1,1,4a-trimethyl-2,3,4,4a,9,9a-hexahydro-1H-xanthene-6,8-diol (4), and two known benzophenones, 4-geranyloxy-2,6-dihydroxybenzophenone (5) and 3-geranyl-2,4,6-trihydroxybenzophenone (6). The structures of 1-4 were established by spectroscopic means and by molecular modeling calculations. Compounds 1 and 3-5 demonstrated cytotoxic activities against breast (MCF-7), central nervous system (SF-268), and lung (H-460) human cancer cell lines, while compounds 3-6 showed antimicrobial activity against Klebsiella pneumoniae, Mycobacterium smegmatis, Pseudomonas aeruginosa, Salmonella gallinarum, and Staphylococcus aureus.
Asunto(s)
Antibacterianos , Antineoplásicos Fitogénicos , Benzofenonas , Clusiaceae/química , Plantas Medicinales/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Benzofenonas/química , Benzofenonas/aislamiento & purificación , Benzofenonas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Mycobacterium smegmatis/efectos de los fármacos , Panamá , Hojas de la Planta/química , Pseudomonas aeruginosa/efectos de los fármacos , Salmonella/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacosRESUMEN
Three new compounds, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl-4,6-bis-O-beta-D-(3,4,5-trihydroxybenzoyl)glucopyranoside (1), 5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-3-yl-5-O-alpha-L-(3,4,5-trihydroxybenzoyl)arabinofuranoside (2), and 2-hydroxy-4-O-alpha-L-(3,5,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenylarabinofuranoside (3), were isolated from the young leaves of Triplaris cumingiana, together with two known compounds, quercetin 3-O-alpha-L-(5"-O-galloyl)arabinofuranoside (4) and quercetin 3-O-beta-D-(6"-O-galloyl)glucopyranoside (5). The structures of 1-3 were established by spectroscopic methods. Compounds 1-5 were evaluated for their cytotoxic activities against the MCF-7, H-460, and SF-268 human cancer cell lines.
Asunto(s)
Flavonoles/aislamiento & purificación , Glicósidos/aislamiento & purificación , Plantas Medicinales/química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Flavonoles/química , Flavonoles/farmacología , Glicósidos/química , Glicósidos/farmacología , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , PanamáRESUMEN
Bioassay-guided fractionation of the CH(2)Cl(2) extract of the leaves of Marila pluricostata led to the isolation of 17 naturally occurring 4-phenylcoumarins, three of them, 5-hydroxy-8,8-dimethyl-4-phenyl-9,10-dihydro-8H-pyrano-[2,3-f]chromen-2-one (1), 5-hydroxy-8,8-dimethyl-4-phenyl-6-propionyl-9,10-dihydro-8H-pyrano-[2,3-f]chromen-2-one (2), and 5,7-dihydroxy-8-(3-methylbut-2-enyl)-4-phenylchromen-2-one (3), are new natural compounds; the remaining (4-17) are known mammea-type coumarins. Their structures were established by spectroscopic means. All compounds were tested in cytotoxicity assays against the MCF-7, H-460, and SF-268 human cancer cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Clusiaceae/química , Cumarinas/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Cumarinas/química , Cumarinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Resonancia Magnética Nuclear Biomolecular , Panamá , Hojas de la Planta/química , Plantas Medicinales/química , Células Tumorales CultivadasRESUMEN
A new cucurbitacin D analogue, 2-deoxycucurbitacin D (1), as well as cucurbitacin D (2) and 25-acetylcucurbitacin F (3) were isolated from Sloanea zuliaensis. Compound 1 was found only in the young leaves of the plant and not in the mature leaves, and its structure was established using spectroscopic means. Compounds 1-3 demonstrated potent cytotoxic activity against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Elaeocarpaceae/química , Plantas Medicinales/química , Triterpenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Neoplasias de la Mama , Neoplasias del Sistema Nervioso Central , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Neoplasias Pulmonares , Estructura Molecular , Panamá , Hojas de la Planta/química , Triterpenos/química , Triterpenos/farmacología , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
In this study, the furofuran lignan (+)-diayangambin [tetrahydro-1,4-bis(3,4,5-trimethoxyphenyl)-(1 R)-1alpha,3abeta,4alpha,6abeta-1 H,3 H-furo [3,4- c]furan] was evaluated in vitro and in vivo for its immunomodulatory and anti-inflammatory efficacy. Human mononuclear cell proliferation was inhibited by diayangambin with an IC 50 value of 1.5 (0.5 - 2.8) microM. In addition, the compound reduced for 40.8 % prostaglandin E 2 generation in stimulated RAW 264.7 macrophage cell line at 10 microM. In vivo, a clear reduction of ear swelling was observed when diayangambin (40 mg/kg) was administered orally to 2,4-dinitrofluorobenzene-treated mice. The inhibition of swelling was associated with a reduction of leukocyte infiltration determined as myeloperoxidase activity. In the carrageenan mouse paw edema model, diayangambin significantly suppressed inflamed paw volume and prostaglandin E 2 levels. Our findings indicate the potential interest of diayangambin in the treatment of immune and inflammatory responses.
Asunto(s)
Anisoles/farmacología , Antiinflamatorios no Esteroideos/farmacología , Furanos/farmacología , Inmunosupresores/farmacología , Inflamación/tratamiento farmacológico , Fitoterapia , Piper , Extractos Vegetales/farmacología , Animales , Anisoles/química , Anisoles/aislamiento & purificación , Antiinflamatorios no Esteroideos/uso terapéutico , Azatioprina/farmacología , Dexametasona/farmacología , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Edema/tratamiento farmacológico , Furanos/química , Furanos/aislamiento & purificación , Inmunosupresores/uso terapéutico , Inflamación/inducido químicamente , Activación de Linfocitos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Ratones , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/uso terapéuticoRESUMEN
Bioassay-guided fractionation of an EtOAc/MeOH extract of Adenaria floribunda young leaves using MCF-7, H-460, and SF-268 cancer cell lines yielded four new active compounds named adenaflorins A-D (1-4). Their chemical structures were determined by spectroscopic means. Adenaflorin A (1) was the most cytotoxic.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Lythraceae/química , Naftoquinonas/aislamiento & purificación , Plantas Medicinales/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Naftoquinonas/química , Naftoquinonas/farmacología , Resonancia Magnética Nuclear Biomolecular , Panamá , Hojas de la Planta/química , Células Tumorales CultivadasRESUMEN
Bioassay-guided fractionation of the methanolic extracts of Vismia baccifera, V. jefensis, and V. macrophylla against human breast, CNS, and lung cancer cell lines resulted in the isolation of a new compound, ferruginin C (1), and seven known compounds, ferruginins A (2) and B (3), vismin (4), harunganin (5), vismione B (6), deacetylvismione H (7), and deacetylvismione A (8), as active constituents. In addition, bivismiaquinone (9) and vismiaquinone (10) were obtained as inactive constituents. The structure of ferruginin C was elucidated by spectroscopic means. Compounds 6-8 were the most active, and the cytotoxic activity of compounds 2-5 and 7 is reported for the first time.
Asunto(s)
Antraquinonas/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Clusiaceae/química , Plantas Medicinales/química , Antraquinonas/química , Antraquinonas/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Neoplasias de la Mama , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Pulmonares , Estructura Molecular , Neoplasias de Tejido Nervioso , Panamá , Hojas de la Planta/química , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
A bioassay-guided fractionation of the 70% acetone extract of the bark of Guazuma ulmifolia Lam. on the inhibition of angiotensin II binding to the AT 1 receptor led to the isolation and identification of bioactive oligomeric and polymeric proanthocyanidins consisting mainly of (-)-epicatechin units. The displacement of [3H]-angiotensin II binding was dose-dependent and correlated with the degree of polymerization of the different fractions containing proanthocyanidins. A strong displacement was seen for the residual fraction suggesting that the most active substances corresponding to the highly polymerized proanthocyanidins. Angiotensin II AT 1 receptor binding might be considered as a potentially interesting biological activity of proanthocyanidins contributing to the very broad spectrum of biological activities of the condensed tannins.
Asunto(s)
Angiotensina II/metabolismo , Antocianinas/farmacología , Malvaceae , Corteza de la Planta/química , Proantocianidinas , Receptores de Angiotensina/metabolismo , Sitios de Unión/efectos de los fármacos , Unión Competitiva/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Extractos Vegetales/farmacología , Receptor de Angiotensina Tipo 1 , Receptores de Angiotensina/efectos de los fármacos , TritioRESUMEN
A bioassay-guided fractionation of the 80 % ethanolic extract from Bocconia frutescens L. roots, showing a dose-dependent inhibitory effect towards both [(3)H]-angiotensin II and [(3)H]-BQ-123 binding to the human angiotensin II AT 1 and endothelin 1 ET(A) receptors, led to an alkaloidal subfraction as the only responsible fraction for the activity of the whole extract. Among the alkaloids present in this fraction sanguinarine and chelerythrine were significant inhibitors of [(3)H]-angiotensin II binding (hAT 1 receptor), with IC(50) values within the micromolar range. On the contrary, the [(3)H]-BQ-123 binding (ET(A) receptor) was only weakly inhibited. Moreover, other members of the isoquinoline alkaloid family such as chelidonine and some protoberberine alkaloids exhibited no affinity for the two receptors. The present work shows the possible structure-activity relationship for these benzophenanthridine alkaloids on a screening bioassay using both stably transfected Chinese hamster ovary (CHO) and the human neuroblastoma SK-N-MC cells. Furthermore, the ability of these compounds to block AT(1) and/or ET(A) receptors may provide some justification for the traditional use of Bocconia frutescens L. to control hypertension.