RESUMO
Twelve new furanocassane diterpenoids, sucupiranins A-L (1-12), and three known compounds (13-15) were isolated from the seeds of Bowdichia virgilioides. The structures of the compounds were elucidated via 1H and 13C NMR analysis, including 2D NMR (1H-1H COSY, HSQC, HMBC, and NOESY); HRMS data; and X-ray crystallographic analysis. The absolute configurations were defined using their electronic circular dichroism (ECD) spectra by applying the exciton chirality method to the bis-p-bromobenzoate of compound 13. Sucupiranin J (10) inhibited lipopolysaccharide-induced nitric oxide production (IC50 30.6 µM), whereas sucupiranins J (10), K (11), and 13 exhibited weak antimalarial activity against Plasmodium falciparum K1 with IC50 values of 32.2, 23.5, and 22.9 µM and selectivity indices of 4.3, 1.9, and >12.0 (MRC-5/K1), respectively.
Assuntos
Diterpenos/química , Fabaceae/química , Sementes/química , Antimaláricos/química , Antimaláricos/farmacologia , Cristalografia por Raios X/métodos , Diterpenos/farmacologia , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Óxido Nítrico/metabolismo , Plasmodium falciparum/efeitos dos fármacosRESUMO
Erythraline, isolated from the bark of Erythrina crista-galli which are used as Brazilian medicine plant for the treatment of inflammation diseases, suppressed nitric oxide (NO) production and induction of inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Because of Toll-like receptor (TLR) 4 and its signal transduction are indispensable to the production of NO and iNOS expression by LPS, we investigated the effects of erythraline on TLR signaling molecules. Western blot analysis revealed that the degradation of inhibitor of nuclear factor (NF)-κB (IκB) by LPS was suppressed by erythraline. Moreover, erythraline inhibited not only LPS-induced phosphorylation of IκB kinase (Ikk) but also phosphorylation of mitogen-activated protein kinases (MAPKs). However, it showed no effect on LPS -induced phosphorylation of transforming growth factor (TGF)-ß-activated kinase (TAK) 1 that exists upstream of Ikk and MAPKs, and is required for the activation of these signaling molecules on TLR signaling pathway. These results suggested that erythraline might have inhibited the kinase activity of TAK1. Furthermore, these results were supported from the inhibitory pattern of erythraline on TLR signaling molecules when the cells were stimulated by TLR2 ligand, peptidoglycan which activates the same pathway as LPS on TLR signal transduction.
Assuntos
Anti-Inflamatórios/farmacologia , Erythrina , Alcaloides Indólicos/farmacologia , MAP Quinase Quinase Quinases/metabolismo , Receptores Toll-Like/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Lipopolissacarídeos , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Peptidoglicano , Casca de Planta , Transdução de Sinais/efeitos dos fármacosRESUMO
Three new indole alkaloids (1-3), named grandilodines A-C, and five known ones were obtained from the Malayan Kopsia grandifolia. The structures were established using NMR and MS analyses and, in the case of 1 and 2, were confirmed by X-ray diffraction analyses. Alkaloids 1, 3, and lapidilectine B (8) were found to reverse multidrug resistance in vincristine-resistant KB cells.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apocynaceae/química , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/farmacologia , Vincristina/farmacologia , Antineoplásicos Fitogênicos/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Alcaloides Indólicos/química , Células KB , Estrutura MolecularRESUMO
Four new bisindole alkaloids of the Strychnos-Strychnos type, leucoridines A-D (1-4), were isolated from the stem-bark extract of Leuconotis griffithii. Alkaloids 1-4 showed moderate cytotoxicity against drug-sensitive and vincristine-resistant human KB cells.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apocynaceae/química , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/farmacologia , Plantas Medicinais/química , Strychnos/química , Antineoplásicos Fitogênicos/química , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Alcaloides Indólicos/química , Células KB , Malásia , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Vincristina/farmacologiaRESUMO
A total of 25 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia spatulata, of which five are new alkaloids of the strychnan type (alstolucines A-E, 1-5) and the other, a new alkaloid of the secoangustilobine A type (alstolobine A, 6). The structures of these alkaloids were established using NMR and MS analysis and, in the case of alstolucine B (2), also confirmed by X-ray diffraction analysis. A reinvestigation of the stereochemical assignment of scholaricine (13) by NMR and X-ray analyses indicated that the configuration at C-20 required revision. Alkaloids 1, 2, 6, 7, 9, 10, and 13 reversed multidrug resistance in vincristine-resistant KB cells.
Assuntos
Alstonia/química , Alcaloides Indólicos/isolamento & purificação , Cristalografia por Raios X , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Células KB , Malásia , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Folhas de Planta/química , Vincristina/farmacologiaRESUMO
Two new Erythrinan alkaloids, cristanines A and B (1, 2), were isolated from the bark of Erythrina crista-galli L. together with nine known Erythrinan alkaloids (3-5, 7-12) and an indole alkaloid (13). The structures of the compounds, cristanines A (1) and B (2), were elucidated by spectroscopic methods. Three of the twelve compounds isolated showed significant inhibitory activity on lipopolysaccharide induced nitric oxide (NO) production.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Erythrina/química , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Alcaloides/isolamento & purificação , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Camundongos , Estrutura Molecular , EstereoisomerismoRESUMO
A new Erythrinan alkaloid (1), erythodine N-oxide, was isolated from the seeds of Erythrina velutina together with seven known Erythrinan alkaloids (2-7, 9) and an indole alkaloid (8). The structure of new compound (1) was elucidated by spectroscopic methods. Six of the nine compounds showed enhanced activity when combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Erysotrine (4) did not show cytotoxic activity by itself, but exhibited significant cytotoxicity when combined with TRAIL.
Assuntos
Alcaloides/farmacologia , Erythrina/química , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/uso terapêutico , Antineoplásicos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Alcaloides Indólicos , Células Jurkat , Estrutura Molecular , Ligante Indutor de Apoptose Relacionado a TNF/uso terapêuticoRESUMO
Seven new indole alkaloids of the Strychnos type, leuconicines A-G (1-7), and a new eburnan alkaloid, (-)-eburnamaline (8), were isolated from the stem-bark extract of two Malayan Leuconotis species. The structures of these alkaloids were established using NMR and MS analysis and in the case of 8 also by partial synthesis. Alkaloids 1-5 reversed multidrug resistance in vincristine-resistant KB cells.
Assuntos
Alcaloides Indólicos/isolamento & purificação , Resistência a Múltiplos Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Células KB , Malásia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Caules de Planta/química , Estereoisomerismo , Vincristina/farmacologiaRESUMO
Berkeleyacetal C (BAC) isolated from Penicillium sp. which had isolated from a soil sample collected in Fukushima, inhibited NO production and induction of iNOS protein in RAW264.7 cells stimulated by the Toll-like receptor (TLR) 2 ligand, peptidoglycan (PGN) or TLR4 ligand, lipopolysaccharide (LPS). The other inflammatory mediator production by these stimulators was also suppressed by BAC in a concentration-dependent manner. BAC inhibited LPS- or PGN-activated nuclear translocation of nuclear factor (NF)-κB and MyD88-dependent signaling molecules. However, it showed no effect on LPS-induced nuclear translocation of interferon regulatory factor (IRF)-3, a MyD88-independent signaling molecule. To clarify the mechanistic basis for BAC ability to inhibit translocation of NF-κB and activated MyD88-dependent signaling molecules, we examined interleukin-1 receptor-associated kinase (IRAK)-4, existing to the most upstream on MyD88-dependent signaling molecules, in vitro kinase assay. BAC suppressed IRAK-4 kinase activity in a concentration-dependent manner. These findings suggest that BAC inhibits LPS- and PGN- induced NO production and iNOS expression by decreasing the level of the translocating of NF-κB in nuclear through inhibiting the kinase activity of IRAK-4 in inflammatory cells.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Terpenos/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/biossíntese , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Fator Regulador 3 de Interferon/metabolismo , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Peptidoglicano/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
A cytotoxic bisindole alkaloid possessing an unprecedented structure constituted from the union of an eburnan half and a novel vinylquinoline alkaloid has been isolated from Leuconotis griffithii. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway to the novel quinolinic coupling partner is presented from an Aspidosperma precursor.