RESUMO
The structures and absolute stereochemistries of tomenphantins A (1) and B (2), cytotoxic germacranolides isolated from Elephantopus tomentosus, are reported herein. 1H and 13C NMR spectroscopic data, chemical transformation, and single-crystal X-ray analysis were used in these determinations.
Assuntos
Antineoplásicos Fitogênicos/química , Furanos/química , Plantas/química , Antineoplásicos Fitogênicos/isolamento & purificação , Cristalografia por Raios X , Furanos/isolamento & purificação , Estrutura Molecular , Análise Espectral , EstereoisomerismoRESUMO
Evaluation of a number of cytotoxic antitumor sesquiterpene lactones and their derivatives has led to the discovery of bis(helenalinyl)glutarate (4) and bis(isoalantodiol-B)glutarate (10) as potent inhibitors of human-derived topoisomerase II. Unlike etoposide, which inhibits by preventing the DNA rejoining process, compounds 4 and 10 inhibit topoisomerase II without causing DNA breakage. The structure-activity relationships of 4, 10, and related compounds are discussed.
Assuntos
Lactonas/farmacologia , Sesquiterpenos/farmacologia , Inibidores da Topoisomerase II , Linhagem Celular , DNA/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Técnicas In Vitro , Lactonas/síntese química , Lactonas/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Sesquiterpenos/síntese química , Sesquiterpenos/química , Relação Estrutura-AtividadeRESUMO
Eight cytotoxic compounds have been isolated from the CHCl3 extract of Amorpha fruticosa. One compound, 6'-O-D-beta-glucopyranosyldalpanol [10], is a new cytotoxic rotenoid. Another known rotenoid, 12 alpha beta-hydroxyamorphigenin [6], was first shown to exhibit extremely potent cytotoxicity (ED50 < 0.001 microgram/ml) in six neoplastic cell lines. In addition to these compounds, three isoflavones (afrormosin [1], 7,2',4', 5'-tetramethoxyisoflavone [2], 8-methylretusin [3]) and five rotenoids (amorphispironone [4], amorphigenin [5], dalpanol [7], 12a beta-hydroxydalpanol [8], and tephrosin [9]) were isolated. Compound 8 was isolated for the first time as a natural product from this plant. The structures of these compounds were established on the basis of spectral data; some were further confirmed by X-ray crystallographic analysis.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Isoflavonas/farmacologia , Plantas Medicinais/química , Rotenona/análogos & derivados , Rotenona/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Carcinoma de Células Escamosas/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isoflavonas/química , Isoflavonas/isolamento & purificação , Neoplasias Laríngeas/tratamento farmacológico , Rotenona/química , Células Tumorais CultivadasRESUMO
A new dammarane triterpene, polacandrin [1], has been isolated from Polanisia dodecandra. The structure of 1 was established as 1 beta, 3 alpha, 12 beta, 25-tetrahydroxy-20(S),24(S)-epoxydammarane by chemical and spectroscopic methods, which included the concerted application of a number of 2D nmr techniques that involved 1H-1H COSY, HETCOR, NOESY, and long-range HETCOR. Single-crystal X-ray analysis of polacandrin pentahydrate verified the complete structure and stereochemistry. Polacandrin showed potent cytotoxicities against KB (ED50 = 0.60 microgram/ml), P-388 (ED50 = 0.90 microgram/ml), and RPMI-7951 (ED50 = 0.62 microgram/ml) tumor cells.
Assuntos
Antineoplásicos Fitogênicos/química , Plantas Medicinais/química , Triterpenos/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Estereoisomerismo , Triterpenos/farmacologia , Células Tumorais Cultivadas , Difração de Raios XRESUMO
The styrylpyrone, goniodiol-7-monoacetate [1] [6R-(7R,8R-dihydro-7-acetoxy-8-hydroxystyryl)-5, 6-dihydro-2-pyrone], has been isolated from Goniothalamus amuyon, and its detailed molecular structure has been determined by X-ray crystallographic analysis. Goniodiol-7-monoacetate showed potent (ED50 values less than 0.1 microgram/ml) cytotoxicities against KB, P-388, RPMI, and TE671 tumor cells.
Assuntos
Antineoplásicos Fitogênicos , Plantas Medicinais , Pironas/farmacologia , Estirenos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Cristalização , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia P388/tratamento farmacológico , Estrutura Molecular , Pironas/química , Pironas/isolamento & purificação , Estirenos/química , Estirenos/isolamento & purificação , Células Tumorais CultivadasRESUMO
Acrovestone was isolated from the stem and root back of Acronychia pedunculata and shown for the first time to be a cytotoxic principle. Its structure, derived from spectral data, was completely characterized by single-crystal X-ray analysis.
Assuntos
Acetofenonas/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Plantas Medicinais/análise , Acetofenonas/farmacologia , Cristalografia , Técnicas de Cultura , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
Two new compounds, cymobarbatol and 4-isocymobarbatol, were isolated from the marine alga Cymopolia barbata. The complete structures and absolute stereochemistries of these compounds were elucidated by a variety of spectroscopic techniques and X-ray crystallography. Both compounds were found to be nontoxic over a broad concentration range to Salmonella typhimurium strains T-98 and T-100. Both compounds exhibited strong inhibition of the mutagenicity of 2-aminoanthracene and ethyl methanesulfonate toward, respectively, the T-98 strain plus a metabolic activator and T-100.
