RESUMO
It is estimated that one-third part of the world population is infected with the tubercle bacillus. While only a small percentage of infected individuals will develop clinical tuberculosis, each year there are approximately eight million new cases and two million deaths. Mycobacterium tuberculosis is thus responsible for more human mortality than any other single microbial species. The goals of tuberculosis control are focused to cure active disease, prevent relapse, reduce transmission and avert the emergence of drug-resistance. For over 50 years, natural products have served us well on combating infectious bacteria and fungi. During the 20th century, microbial and plant secondary metabolites have helped to double our life span, reduced pain and suffering, and revolutionized medicine. Colombia is a megadiverse country with enormous potential to offer leads for new antimycobacterial drugs. The principal aim of this article is to show a state of the art on antimycobacterial natural products research in Colombia compared to the rest of the world, in order to develop programs for bioprospecting with a view to determining the biological activity for pharmaceutical and industrial application of natural products in our country.
Assuntos
Antituberculosos/farmacologia , Produtos Biológicos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Animais , Biodiversidade , Colômbia , Fungos , Humanos , Insetos , Biologia Marinha , Plantas/química , Tuberculose/epidemiologiaRESUMO
Introducción. El efecto contra la proliferación celular de once neolignanos, dos lignanos y un diterpeno, aislados de tres plantas de la familia Lauraceae, y cuatro benzofuranos y dos biciclooctanos sintéticos, fue evaluado in vitro sobre cinco líneas celulares derivadas de tumores sólidos de alta incidencia en Colombia.Objetivo. Evaluar el efecto citotóxico de veinte compuestos sobre las líneas tumorales HeLa, A-549, Hep-2, PC-3 y MCF-7. Materiales y métodos. Los 14 compuestos de origen natural fueron aislados de tres plantas nativas colombianas (Pleurothyrium cinereum, Ocotea macrophylla y Nectandra amazonum) por técnicas cromatográficas y se establecieron sus estructuras por métodos espectroscópicos, y los seis derivados sintéticos fueron preparados mediante reacción de oxiarilación y metilación con diazometano. El efecto contra la proliferación y la recuperación celular se hicieron mediante tratamiento in vitro de las líneas tumorales con los compuestos , evaluando la viabilidad celular por tinción con resazurina.Resultados. Entre los compuestos evaluados, solamente ocofilal A, cinerina D, ácido kaurenoico, dos benzofuranos y la (-)-cinerina A sintética presentaron actividad contra la proliferación celular en diferentes niveles. Los biciclooctanos, así como el ácido kaurenoico, fueron activos contra todas las líneas celulares, mientras que los benzofuranoides mostraron actividad selectiva contra HeLa. Además, la (-)-cinerina A exhibió un efecto letal total contra todas las líneas celulares, mientras que el ácido kaurenóico presentó efecto letal total contra PC-3, Hep-2 y A549.Conclusión. Los compuestos evaluados que exhibieron actividad contra la proliferación celular mostraron resultados interesantes, lo cual sugiere su potencial uso como cabezas de serie o moléculas plantilla en el desarrollo de agentes anticancerígenos.
Introduction. The antiproliferative effect of eleven neolignans, two lignans and one diterpene isolated from three Lauraceae plants, four benzofurans and two bicyclooctanes synthetic derivatives was evaluated in vitro on a set of five human cancer cells from solid tumors with a high incidence in Colombia.Objective. To evaluate the cytotoxic effect of twenty compounds on the tumor cell lines HeLa, A-549, Hep-2, PC-3, and MCF-7.Materials and methods. Fourteen natural compounds were isolated by chromatographic techniques from three native colombian plants (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), whose structures were established by spectroscopic methods; six synthetic derivatives were prepared by oxyarylation and diazomethane methylation. Antiproliferative effect and cell recovery were performed by means of in vitro treatment of tumor cell lines with test compounds, evaluating cell viability by resazurin staining.Results. Among test compounds, only neolignans ocophyllal A, cinerin D, kaurenoic acid, two benzofuran-derivatives, and synthetic (-)-cinerin A were found to have antiproliferative effect at different levels. Bicyclooctanoids as well as kaurenoic acid exhibited activity against all human cancer cells while benzofuranoids showed selective activity against HeLa. Furthermore, compounds (-)-cinerin A and kaurenoic acid exhibited total lethal effect against all-five cell lines and PC-3, Hep-2, and A549 cell lines, respectively.Conclusion. Test compounds exhibiting antiproliferative activity showed interesting results, which would promote their use as lead compounds on further studies for anticancer agents development.
Assuntos
Diterpenos , Lauraceae , Peneiramento de Líquidos , Plantas/toxicidadeRESUMO
INTRODUCTION: The antiproliferative effect of eleven neolignans, two lignans and one diterpene isolated from three Lauraceae plants, four benzofurans and two bicyclooctanes synthetic derivatives was evaluated in vitro on a set of five human cancer cells from solid tumors with a high incidence in Colombia. OBJECTIVE: To evaluate the cytotoxic effect of twenty compounds on the tumor cell lines HeLa, A-549, Hep-2, PC-3, and MCF-7. MATERIALS AND METHODS. Fourteen natural compounds were isolated by chromatographic techniques from three native Colombian plants (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), whose structures were established by spectroscopic methods; six synthetic derivatives were prepared by oxyarylation and diazomethane methylation. Antiproliferative effect and cell recovery were performed by means of in vitro treatment of tumor cell lines with test compounds, evaluating cell viability by resazurin staining. RESULTS: Among test compounds, only neolignans ocophyllal A, cinerin D, kaurenoic acid, two benzofuran-derivatives, and synthetic (-)-cinerin A were found to have antiproliferative effect at different levels. Bicyclooctanoids as well as kaurenoic acid exhibited activity against all human cancer cells while benzofuranoids showed selective activity against HeLa. Furthermore, compounds (-)-cinerin A and kaurenoic acid exhibited total lethal effect against all-five cell lines and PC-3, Hep-2, and A549 cell lines, respectively. CONCLUSION: Test compounds exhibiting antiproliferative activity showed interesting results, which would promote their use as lead compounds on further studies for anticancer agents development.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Citotoxinas/isolamento & purificação , Lauraceae/química , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Benzofuranos/síntese química , Benzofuranos/farmacologia , Compostos Bicíclicos com Pontes/isolamento & purificação , Compostos Bicíclicos com Pontes/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Colômbia , Citotoxinas/síntese química , Citotoxinas/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lignanas/isolamento & purificação , Lignanas/farmacologia , Estrutura Molecular , Ocotea/química , Extratos Vegetais/química , Relação Estrutura-AtividadeRESUMO
The anti-inflammatory potential of 26 neolignans (14 of the bicyclooctane-type and 12 of the benzofuran-type), isolated from three Lauraceae species (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), was evaluated in vitro through inhibition of COX-1, COX-2, 5-LOX and agonist-induced aggregation of rabbit platelets. Benzofuran neolignans were found to be selective COX-2 inhibitors, whereas bicyclooctane neolignans inhibit selectively the PAF-action as well as COX-1 and 5-LOX. The neolignan 9-nor-7,8-dehydro-isolicarin B 15 and cinerin C 7 were found to be the most potent COX-2 inhibitor and PAF-antagonist, respectively. Nectamazin C 10 exhibited dual 5-LOX/COX-2 inhibition.