RESUMO
After removing lipophilic material, the ground root bark of Quassia africana Baill. (Simaroubaceae) was extracted with ethanol 95 %. Partitioning between chloroform, ethyl acetate and water yielded three crude extracts. Pronounced activities were shown by the chloroform and ethyl acetate crude extracts against Herpes simplex, Semliki forest, Coxsackie and Vesicular stomatitis viruses. By repeated column chromatography and preparative thin layer chromatography on silica gel, two quassinoids, i. e., quassin and simalikalactone D were isolated. Structures of the pure compounds were established primarily using NMR spectroscopy. Mass spectral information confirmed the assigned structures. Simalikalactone D was responsible, at least in part, for the high antiviral activity observed for the chloroform crude extract. Quassin showed no activity. For quassinoids the ester group at C-15 and the epoxymethano bridge between C-8 and C-13 appeared to be important structural features in order to exhibit a pronounced antiviral activity.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antivirais/farmacologia , Glaucarubina/análogos & derivados , Glaucarubina/farmacologia , Quassinas , Simaroubaceae , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Glaucarubina/química , Glaucarubina/isolamento & purificação , Herpesvirus Humano 1/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Medicinas Tradicionais Africanas , Estrutura Molecular , Casca de Planta/química , Extratos Vegetais/farmacologia , Raízes de Plantas/químicaRESUMO
Four quassinoids, indaquassin C (1), samaderins C (2), B (3) and A (4), isolated from the seeds and bark of Samadera indica, were tested for insect antifeedant and growth regulatory activities against the tobacco cutworm, Spodoptera litura. Indaquassin C was the most effective antifeedant. Samaderin C increased pupal duration and induced pupal mortality.
Assuntos
Comportamento Alimentar/efeitos dos fármacos , Glaucarubina/farmacologia , Inseticidas/farmacologia , Quassinas , Rosales , Spodoptera/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Glaucarubina/análogos & derivados , Glaucarubina/química , Inseticidas/química , Larva/efeitos dos fármacos , Caules de Planta , Sementes , Triterpenos/químicaRESUMO
In an effort to discover new chemotherapeutic/chemopreventive agents from natural sources, brusatol (1) was found to induce HL-60 cellular differentiation, accompanied by strong antiproliferative and cytotoxic effects. A series of natural and semisynthetic quassinoids (1-48) was designed to effect both antiproliferative and differentiation-inducing properties. Compounds were assessed in vitro using the HL-60 promyelocytic cell model. Changes in activity due to structural modification of the core structure glaucarubolone (24) were consistent with activities reported in other cell systems. However, the following were novel SAR findings: (1) semisynthetic analogues with a hydroxylated ring at the beta-position of the ester side chain at C-15 were able to induce cellular differentiation at concentrations lower than those inducing cell growth arrest, and (2) quassinoids inhibiting DNA synthesis with greater efficacy than reducing cellular viability possessed alkyl substitutions at the alpha-position of the C-15 ester side chain. Analogues from this latter group and brusatol (1) and bruceantin (2) inhibited dimethylbenz(a)anthracene-induced preneoplastic lesion formation in a mouse mammary organ culture. The novel finding of 1 and glaucarubolone analogues as potent inducers of differentiation leads to potential novel applications in the field of cancer.
Assuntos
9,10-Dimetil-1,2-benzantraceno/antagonistas & inibidores , Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/síntese química , Diferenciação Celular/efeitos dos fármacos , Glaucarubina/análogos & derivados , Glaucarubina/síntese química , Neoplasias Mamárias Animais/induzido quimicamente , Plantas Medicinais/química , Quassinas , Simaroubaceae/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Divisão Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , DNA/efeitos dos fármacos , DNA/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glaucarubina/química , Glaucarubina/farmacologia , Glicosilação , Células HL-60/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Modelos Biológicos , Estrutura Molecular , Nitroazul de Tetrazólio/farmacologia , Técnicas de Cultura de Órgãos , Ratos , Relação Estrutura-Atividade , Fatores de Tempo , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The structures of six new C20 quassinoids and one new C19 quassinoid, all isolated from the twigs and thorns of Castela polyandra, were established by a combination of spectroscopic and single-crystal X-ray analysis. Five known quassinoids and one known sterol were also identified.
Assuntos
Glaucarubina/análogos & derivados , Plantas Medicinais/química , Glaucarubina/química , Glaucarubina/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Difração de Raios XRESUMO
Hannoa chlorantha and Hannoa klaineana (Simaroubaceae) are used in traditional medicine of Central African countries against fevers and malaria. Four stem bark extracts from H. klaineana and four quassinoids from H. chlorantha were examined in vitro against Plasmodium falciparum NF 54. The extracts displayed good activities, while the quassinoids were highly active, with IC50 values well below 1 microgram ml-1, those of chaparrinone and 15-desacetylundulatone being much lower than 0.1 microgram ml-1 (0.037 and 0.047 microgram ml-1, respectively). Chaparrinone is five times more active than 14-hydroxychaparrinone against P. falciparum, indicating that the hydroxyl function at C-14 is unfavourable for antiplasmodial activity. As 14-hydroxychaparrinone has a seven-times higher cytotoxic activity against P-388 cells than chaparrinone, the latter compound has the better antiplasmodial therapeutic index. All four quassinoids were evaluated in vivo in a standard 4-day test as well. 15-Desacetylundulatone was proven to be the most active compound, almost totally suppressing the parasitaemias of OF1 mice for at least 7 days, while both chaparrinone and 14-hydroxychaparrinone were active for at least 4 days. Quassinoids have ED50 values much lower than 50 mg kg-1 body weight day-1 and none of them caused obvious side effects. The keto function at C-2 in 15-desacetylundulatone is apparently of crucial importance for its high activity. 6-alpha-Tigloyloxyglaucarubol was not active at all. Chaparrinone is considered the most interesting of the investigated quassinoids and its in-vivo antimalarial potential will be examined further.
Assuntos
Antimaláricos/farmacologia , Malária/tratamento farmacológico , Extratos Vegetais/farmacologia , Plantas Medicinais , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Quassinas , Animais , Antimaláricos/química , Antimaláricos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Feminino , Glaucarubina/análogos & derivados , Glaucarubina/química , Glaucarubina/farmacologia , Glaucarubina/toxicidade , Leucemia P388 , Camundongos , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Raízes de Plantas/química , Plantas Medicinais/química , Sementes/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Four new quassinoids named samaderines X (1), Y (2) and Z (3), and indaquassin X (5), and a new C19 quassinoid glycoside, 2-O-glucosylsamaderine C (10), together with five known quassinoids, samaderines B (7), C (8), and E (4), indaquassin C (6), and simarinolide (9), were isolated form the stems of Quassia indica (Simaroubaceae), an Indonesian medicinal plant. The chemical structures of these quassinoids have been elucidated on the bases of their chemical and physiochemical properties. Samaderines X (1), Z (3), E (4), and B (7) were shown to exhibit significant growth-inhibitory activity against the cultured malarial parasite Plasmodium falciparum (a chloroquine- resistant K1 strain), and 1--8 were shown to exhibit in vitro cytotoxicity (IC50: 0.04--100 micrograms/ml) against KB cells. Samaderines X (1), B (7) and C (8), as well s indaquassin X (5), exhibited inhibitory activity in the in vitro endothelial cell-neutrophil leukocyte adhesion assay, whereas samaderines X (1) and B (7) were found to exhibit significant anti-inflammatory activity.
Assuntos
Antimaláricos/química , Antineoplásicos Fitogênicos/química , Glaucarubina/análogos & derivados , Caules de Planta/química , Plantas Medicinais/química , Quassinas , Animais , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Glaucarubina/química , Glaucarubina/farmacologia , Humanos , Hidrólise , Indonésia , Células KB , Espectroscopia de Ressonância Magnética , Conformação Molecular , Plasmodium falciparum/efeitos dos fármacos , Células Tumorais CultivadasAssuntos
Amebicidas/farmacologia , Entamoeba histolytica/efeitos dos fármacos , Glaucarubina/análogos & derivados , Masoprocol/farmacologia , Quassinas , Acetilação , Amebicidas/química , Animais , Fenômenos Químicos , Físico-Química , Entamoeba histolytica/crescimento & desenvolvimento , Glaucarubina/química , Glaucarubina/farmacologia , Masoprocol/análogos & derivados , Masoprocol/química , Extratos Vegetais/farmacologia , Raízes de Plantas/químicaRESUMO
Bruceoside C [5], a new quassinoid glucoside, and related compounds were isolated from Brucea javanica, and their structures were elucidated by spectral data. Bruceoside C showed potent cytotoxicities against KB, A-549, RPMI, and TE-671 tumor cells.