RESUMO
The extracts and 12 sesquiterpenes obtained from the East African medicinal plant Warburgia ugandensis Sprague (Canellaceae) were assessed for their antiplasmodial activity against the chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum and antitrypanosomal activity against Trypanosoma brucei rhodesiense. The dichloromethane extract displayed strong antiplasmodial and antitrypanosomal activities with IC(50) values of 8.10 and 1.10 µg/mL against K1 strain of the malaria parasite and STlB900 strain of T. b. rhodesiense, respectively. Among the compounds evaluated for inhibition of trypomastigotes, both drimane and coloratane sesquiterpenes possessing aldehyde groups at positions 8 and 9 were found to show most antitrypanosomal activity with IC(50) values in the range 0.56-6.4 µM. The antiplasmodial assays also revealed that the six coloratane and six drimane sesquiterpenes isolated from this extract exhibited significant antitrypanosomal activity with IC(50) values ranged from 0.45 to ?114 µM. Among the compounds tested against the malarial parasite P. falciparum 11?-hydroxymuzigadiolide (3) was most active with an IC(50) value of 6.40 µM.
Assuntos
Antiprotozoários/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Sesquiterpenos/farmacologia , Trypanosoma brucei rhodesiense/efeitos dos fármacos , Antiprotozoários/isolamento & purificação , Concentração Inibidora 50 , Magnoliopsida/química , Estrutura Molecular , Testes de Sensibilidade Parasitária , Casca de Planta/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Sesquiterpenos Policíclicos , Sesquiterpenos/isolamento & purificaçãoRESUMO
The stem bark of Discopodium penninervium afforded a withanolide, 6alpha,7alpha-epoxy-1-oxo-5alpha,12alpha,17alpha-trihydroxywitha-2,24-dienolide (1) and a coloratane sesquiterpene, 7alpha,11alpha-dihydroxy-4(13),8-coloratadien-12,11-olide (4) along with five known compounds, withanone (2), 5alpha,17beta-dihydroxy-6alpha,7alpha-epoxy-1-oxowitha-2,24-dienolide (3), 7alpha,11alpha-dihydroxy-8-drimen-12,11-olide (5), withasomnine (6), and (E,Z)-9-hydroxyoctadeca-10,12-dienoic acid (7). The identity of the compounds was established on the basis of spectroscopic data analysis. All compounds were assessed for inhibition of leukotriene metabolism in an in vitro bioassay using activated human neutrophile granulocytes, and for in vitro cycloxygenase-1 and -2 inhibition from sheep cotyledons and seminal vesicles, respectively. In the leukotriene biosynthesis assay all compounds tested at a concentration of 50 microM exhibited activity with percentage inhibitions ranging from 11.5 to 36.6. The withanolide, 1, displayed a 46.4% inhibition of COX-2 and a 22.9% inhibition of LTB(4) formation at 50 microM concentration. Compounds 4 and 6 inhibited LTB(4) biosynthesis but showed minor inhibition of COX-1 and COX-2. The remaining compounds, on the other hand, were found to be inactive on COX enzymes.
Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Antagonistas de Leucotrienos/farmacologia , Casca de Planta/química , Solanaceae/química , Animais , Células Cultivadas , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/química , Humanos , Antagonistas de Leucotrienos/química , Leucotrieno B4/antagonistas & inibidores , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Vitanolídeos/química , Vitanolídeos/farmacologiaRESUMO
Seven geranylated furocoumarins were isolated from the fruits of TETRADIUM DANIELLII (Benn.) T.G. Hartley (Rutaceae) and tested for their antimycobacterial activity against MYCOBACTERIUM FORTUITUM, M. SMEGMATIS and M. PHLEI. They were shown to be highly active, with minimal inhibitory concentrations (MICs) ranging from 8 to 64 microg/mL. Xanthotoxin and xanthotoxol, representing furocoumarins lacking the lipophilic geranyl side chain, were tested similarly and were shown to be inactive. Geraniol alone was inactive as well. The antimycobacterial activity of the substances was dependent on the position and polarity of the geranyl moiety. The compounds were purified using chromatographic methods. Structure elucidation was achieved with 1D and 2D NMR experiments.
Assuntos
Antibacterianos/análise , Furocumarinas/química , Mycobacterium , Rutaceae/química , Frutas/química , Furocumarinas/isolamento & purificação , Estrutura MolecularRESUMO
Twelve drimane and coloratane sesquiterpenes, isolated from the stem bark of Ethiopian Warburgia ugandensis, were evaluated for inhibition of 12( S)-HETE using human platelets and of leukotriene B (4) formation using activated human neutrophile granulocytes. Among the compounds examined for inhibition of 12-LOX, ugandensidial and muzigadial displayed potent inhibitory activity with IC (50) values of 3.3 and 20.2 microM, respectively, in comparison to the positive control baicalein with an IC (50) value of 20.0 microM. In the 5-LOX assay muzigadial and ugandensidial also exhibited a dose dependent and potent inhibitory effect on LTB (4) biosynthesis with an IC (50) value of 10.2 and 12.7 microM, respectively, compared to the well known 5-LOX inhibitor zileuton with an IC (50) value of 10.4 microM. In contrast, none of the other sesquiterpenoids showed significant inhibition of either 12( S)-HETE or LTB (4) metabolism.
Assuntos
Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/antagonistas & inibidores , Plaquetas/metabolismo , Sequestradores de Radicais Livres/farmacologia , Leucotrienos/metabolismo , Magnoliopsida , Fitoterapia , Extratos Vegetais/farmacologia , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Concentração Inibidora 50 , Leucotrieno B4/biossíntese , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Caules de Planta , Sesquiterpenos/administração & dosagem , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêuticoRESUMO
During the course of screening Ethiopian medicinal plants for their antimalarial properties, it was found that the dichloromethane extract of the roots of Kniphofia foliosa Hochst. (Asphodelaceae), which have long been used in the traditional medicine of Ethiopia for the treatment of abdominal cramps and wound healing, displayed strong in vitro antiplasmodial activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum with an ED50 value of 3.8 microg/mL and weak cytotoxic activity against KB cells with an ED50 value of 35.2 microg/mL. Five compounds were isolated from the roots and evaluated for their in vitro antimalarial activity. Among the compounds tested, 10-(chrysophanol-7'-yl)-10-(xi)-hydroxychrysopanol-9-anthrone and chryslandicin, showed a high inhibition of the growth of the malaria parasite, P. falciparum with ED50 values of 0.260 and 0.537 microg/mL, respectively, while the naphthalene derivative, 2-acetyl-1-hydroxy-8-methoxy-3-methylnaphthalene, exhibited a less significant antimalarial activity with an ED50 value of 15.4 microg/mL. To compare the effect on the parasite with toxicity to mammalian cells, the cytotoxic activities of the isolated compounds against the KB cell line were evaluated and 10-(chrysophanol-7'-yl)-10-(xi)-hydroxychrysopanol-9-anthrone and chryslandicin displayed very low toxicity with ED50 values of 104 and 90 microg/mL, respectively. This is the first report of the inhibition of the growth of P. falciparum by anthraquinone-anthrone dimers and establishes them as a new class of potential antimalarial compounds with very little host cell toxicity.
Assuntos
Antimaláricos/farmacologia , Liliaceae , Malária Falciparum/prevenção & controle , Fitoterapia , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Cloroquina , Resistência a Medicamentos , Humanos , Células KB , Testes de Sensibilidade Parasitária , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Plasmodium falciparum/classificaçãoAssuntos
Alcaloides/farmacologia , Antibacterianos/isolamento & purificação , Evodia/química , Mycobacterium/efeitos dos fármacos , Quinolonas/farmacologia , Alcaloides/isolamento & purificação , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Quinolonas/isolamento & purificaçãoRESUMO
Platelet 12-lipoxygenase is believed to play a role in cancer and other pathological conditions, such as psoriasis, atherosclerosis and arthritis. The inhibition of 12-LOX is a potential therapeutic approach in the treatment of tumor metastasis. The extracts of Euclea racemosa Murr. ssp. schimperi (A. DC.) F. White (Ebenaceae) obtained by maceration and naphthoquinones isolated from the dichloromethane extract have been investigated for their 12(S)-HETE inhibitory activity using human platelets. At 100 microg/ml, the dichloromethane extract inhibited the formation of 12(S)-HETE by 88.7% and compounds 7-methyljuglone (2), isodiospyrin (3), neodiospyrin (4) and mamegakinone (5), isolated from this extract, exhibited significant activities with IC(50) values ranging from 4 to 58 microg/ml (22.2-155.7 microM). Of these the most abundant compound, 7-methyljuglone displayed a potent inhibitory activity with an IC(50) value of 4.18 microg/ml (22.2 microM), which was comparable to the positive control baicalein with an IC(50) value of 5 microg/ml (18.5 microM). In contrast, 4(S)-shinanolone (1), the reduced form of compound 2, did not show any significant inhibitory activity even at a concentration of 60 microg/ml.