RESUMO
UNLABELLED: The search for new anti-cancer drugs is one of the most prominent research areas of natural products. Numerous active compounds isolated from Brazilian Cerrado plant species have been studied with promising results. AIM OF THE STUDY: To investigate the cytotoxic potential of 412 extracts from Brazilian Cerrado plants used in traditional medicine belonging to 21 families against tumor cell lines in culture. MATERIAL AND METHOD: Maceration of 50 plant species resulted in 412 hexane, dichloromethane, ethanol and hydroalcohol extracts. The cytotoxicity of the extracts was tested against human colon carcinoma (HCT-8), melanoma (MDA-MB-435), and brain (SF-295) tumor cell lines, using the thiazolyl blue test (MTT) assay. Bioassay-guided fractionation was performed for one active extract. RESULTS AND CONCLUSIONS: Twenty-eight of the 412 tested extracts demonstrated a substantial antiproliferative effect, at least 85% inhibition of cell proliferation at 50 microg/mL against one or more cell lines. Those extracts are obtained from different parts of Anacardiaceae, Annonaceae, Apocynaceae, Clusiaceae, Flacourtiaceae, Sapindaceae, Sapotaceae, Simaroubaceae and Zingiberaceae. Complete dose-response curves were generated and IC(50) values were calculated for these active extracts against four cell lines HCT-8, MDA-MB-435, SF-295 and HL-60 (leukemia), and their direct cytotoxic effects were determined. In summary, 14 extracts of 13 species showed toxicity in all tested tumor cell lines, with IC(50) values ranging from 0.1 to 19.1 microg/mL. The strongest cytotoxic activity was found for the hexane extract of Casearia sylvestris var. lingua stem bark, with an IC(50) of 0.1 microg/mL for HCT-8, 0.9 microg/mL for SF-295, 1.2 microg/mL for MDA-MB-435, and 1.3 microg/mL for HL-60, and Simarouba versicolor root bark, with an IC(50) of 0.5 microg/mL for HCT-8, 0.7 microg/mL for SF-295, 1.5 microg/mL for MDA-MB-435, 1.1 microg/mL for HL-60. Bioassay-guided fractionation of the last extract led to the isolation of glaucarubinone, which showed pronounced activity against the four cell lines studied. Further studies of the active extracts are necessary for chemical characterization of the active compounds and more extensive biological evaluations.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Magnoliopsida/química , Medicina Tradicional , Neoplasias/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Antineoplásicos Fitogênicos/farmacologia , Brasil , Casearia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ecossistema , Glaucarubina/análogos & derivados , Glaucarubina/isolamento & purificação , Glaucarubina/farmacologia , Glaucarubina/uso terapêutico , Humanos , Concentração Inibidora 50 , Extratos Vegetais/farmacologia , Estruturas Vegetais , SimaroubaRESUMO
Cedronin was isolated from Simaba cedron Planchon (Simaroubaceae), a species popularly believed in South America to have antimalarial properties. It was examined for in vitro and in vivo antimalarial activities and for cytotoxicity against KB cells. Experimental results showed that cedronin was active against chloroquine-sensitive and resistant strain, with an IC50 of 0.25 micrograms/ml (0.65 mumol/ml). It was also found to be active in vivo against Plasmodium vinkei with an IC50 of 1.8 mg/kg (4.7 nM/kg) in the classic 4-day test. Cedronin belongs to the small group of quassinoids with a C19 basic skeleton and shows a rather low cytotoxicity against KB cells (IC50 = 4 micrograms/ml, 10.4 microM) as compared with C20 biologically active quassinoids; however its toxic/therapeutic ratio (10/1.8) remains lower than chloroquine (10/0.5).
Assuntos
Antimaláricos/farmacologia , Glaucarubina/análogos & derivados , Malária/tratamento farmacológico , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Quassinas , Animais , Antimaláricos/uso terapêutico , Antimaláricos/toxicidade , Cloroquina/farmacologia , Resistência a Medicamentos , Glaucarubina/farmacologia , Glaucarubina/uso terapêutico , Glaucarubina/toxicidade , Humanos , Técnicas In Vitro , Células KB , Masculino , Camundongos , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Plasmodium/efeitos dos fármacos , Plasmodium falciparum/crescimento & desenvolvimentoRESUMO
Two antimalarial quassinoids, gutolactone [1] and simalikalactone D [2], have been characterized by bioactivity-directed fractionation from the bark of Simaba guianensis collected near Manaus, Brazil. Compound 2 was previously isolated from Simaba multiflora and Quassia africana and shown to be an active antimalarial in vitro. This is the first occurrence of 1. The structure of the novel quassinoid was established by spectral methods including 2D nmr spectroscopy.
Assuntos
Antimaláricos/isolamento & purificação , Compostos Bicíclicos com Pontes/isolamento & purificação , Glaucarubina/análogos & derivados , Plantas Medicinais/química , Quassinas , Animais , Antimaláricos/farmacologia , Brasil , Compostos Bicíclicos com Pontes/farmacologia , Cromatografia em Camada Fina , Glaucarubina/isolamento & purificação , Glaucarubina/farmacologia , Espectroscopia de Ressonância Magnética , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Espectrofotometria UltravioletaRESUMO
Two new quassinoids, 13, 18-dehydro-6 alpha-senecioyloxychaparrin (4) and 12-dehydro-6 alpha-senecioyloxychaparrin (5), have been isolated from Simaba multiflora fruits. Their structures were deduced from spectral data. 1H-13C 2-D chemical-shift correlation nmr was applied to the structural elucidation of the antileukemic quassinoid 4.