RESUMO
A novel trimeric monoterpenoid indole alkaloid, vincarostine A (1) consisting of an aspidosperma-iboga-aspidosperma type skeleton, was isolated from the whole plant of Catharanthus roseus. The structure including absolute stereochemistry was elucidated on the basis of 2D NMR data and CD spectrum. Vincarostine A (1) showed anti-malarial activity.
Assuntos
Antimaláricos , Catharanthus , Alcaloides de Triptamina e Secologanina , Catharanthus/química , Antimaláricos/química , Antimaláricos/farmacologia , Estrutura Molecular , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Espectroscopia de Ressonância Magnética , Plasmodium falciparum/efeitos dos fármacos , Extratos Vegetais/químicaRESUMO
Oxomollugin is a degraded product of mollugin and was found to be an active compound that inhibits LPS-induced NF-κB activation. In this study, we investigated the inhibitory activity of oxomollugin, focusing on TLR4 signaling pathway, resulting in NF-κB activation. Oxomollugin inhibited the LPS-induced association of essential factors for initial activation of TLR4 signaling, MyD88, IRAK4 and TRAF6. Furthermore, oxomollugin showed suppressive effects on LPS-induced modification of IRAK1, IRAK2 and TRAF6, LPS-induced association of TRAF6-TAK1/TAB2, and followed by IKKα/ß phosphorylation, which critical in signal transduction leading to LPS-induced NF-κB activation. The consistent results suggested that oxomollugin inhibits LPS-induced NF-κB activation via the suppression against signal transduction in TLR4 signaling pathway.The activities of oxomollugin reported in this study provides a deeper understanding on biological activity of mollugin derivatives as anti-inflammatory compounds.
Assuntos
Lipopolissacarídeos , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Camundongos , Humanos , Células RAW 264.7 , Fosforilação/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , Lactonas , Resorcinóis , Zearalenona/administração & dosagemRESUMO
A new dimeric indole alkaloid, vincazalidine A consisting of an aspidosperma type and a modified iboga type with 1-azatricyclo ring system consisting of one azepane and two piperidine rings coupled with an oxazolidine ring was isolated from Catharanthus roseus, and the structure including absolute stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Vincazalidine A induced G2 arrest and subsequent apoptosis in human lung carcinoma cell line, A549 cells.
Assuntos
Alcaloides , Antineoplásicos , Aspidosperma , Catharanthus , Humanos , Catharanthus/química , Catharanthus/metabolismo , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/química , Aspidosperma/química , Aspidosperma/metabolismoRESUMO
A dimeric indole alkaloid, isovincathicine consisting of an aspidosperma type and modified iboga with C-7-C-20 connection type skeletons was first isolated from Catharanthus roseus, and the structure including stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Isovincathicine inhibited cell proliferation in A549 cells. We investigated the detailed mode of action of isovincathicine-induced inhibitory effects on cell proliferation in A549 cells. Flow cytometric analysis showed that isovincathicine-treated cells accumulated in the G2 phase after 24 h, and the percentage of cells showing cell death increased after 48 h. Western blotting also showed increased expression of BimEL, an apoptosis-related protein, and decreased expression of Mcl-1 and Bcl-xL. Isovincathicine was suggested to induce apoptosis in A549 cells by a mechanism is similar to that of vinblastine.
Assuntos
Catharanthus , Humanos , Catharanthus/química , Catharanthus/metabolismo , Células A549 , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/química , ApoptoseRESUMO
Ceramicines are a series of limonoids which were isolated from the barks of Malaysian Chisocheton ceramicus (Meliaceae), and were known to show various biological activity. Six new limonoids, ceramicines U-Z (1-6), with a cyclopentanone[α]phenanthrene ring system with a ß-furyl ring at C-17 were isolated from the barks of C. ceramicus. Their structures were determined on the basis of the 1D and 2D NMR analyses, and their absolute configurations were investigated by CD spectroscopy. Ceramicine W (3) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 1.2 µM. In addition, the structure-antimalarial activity relationship (SAR) of the ceramicines was investigated to identify substituent patterns that may enhance activity. It appears that ring B and the functional groups in the vicinity of rings B and C are critical for the antimalarial activity of the ceramicines. In particular, bulky ester substituents with equatorial orientation at C-7 and C-12 greatly increase the antimalarial activity.
Assuntos
Antimaláricos , Limoninas , Meliaceae , Antimaláricos/farmacologia , Limoninas/química , Relação Estrutura-Atividade , Espectroscopia de Ressonância Magnética , Meliaceae/química , Estrutura MolecularRESUMO
Ceramicines are a series of limonoids that were isolated from the bark of Malaysian Chisocheton ceramicus (Meliaceae) and were known to show various biological activity. Four new limonoids, ceramicines Q-T (1-4) were isolated from the barks of C. ceramicus, and their structures were determined on the basis of the 1D and 2D NMR analyses in combination with calculated 13C chemical shift data. Ceramicines Q-T (1-4) were established to be new limonoids with a cyclopentanone[α]phenanthren ring system with a ß-furyl ring at C-17, and without a tetrahydrofuran ring like ceramicine B, which is characteristic of known ceramicines. Ceramicine R (2) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 2.8 µM.
Assuntos
Antimaláricos , Limoninas , Meliaceae , Antimaláricos/farmacologia , Limoninas/química , Espectroscopia de Ressonância Magnética , Plasmodium falciparum , Meliaceae/químicaRESUMO
A new C27N3-type Lycopodium alkaloid consisting of two decahydroquinolines and a piperidine, cryptadine C (1) was isolated from Lycopodium cryptomerinum. The structure and relative configuration of 1, which is related to those of cryptadines A and B, lycoperine A, and hupercumine A, was elucidated on the basis of spectroscopic data. Cryptadine C showed moderate inhibitory activity against acetylcholinesterase.
Assuntos
Alcaloides , Lycopodium , Lycopodium/química , Acetilcolinesterase , Alcaloides/farmacologia , Alcaloides/químicaRESUMO
Benign prostate hyperplasia (BPH) is an enlargement of the prostate gland, because of hormonal changes in aging males which contribute significantly to excessive proliferation over apoptosis of prostatic cells. The anti-proliferative and induced apoptotic activities of Eurycoma longifolia quassinoids on cancer cell lines could be promising therapeutic targets on BPH. Hitherto, no report of the quassinoids against BPH problem was available. In this study, a systematic phytochemical fractionation of the root extract, TAF2 was performed, which led to the discovery of nine previously described C20 quassinoids (1-9). Two undescribed C20 (10 and 12) and one undescribed (11) C19 quassinoids were identified by detailed NMR and HR-ESI-MS data analysis. Their absolute configurations were assigned by ECD spectral analysis. The quassinoids (1-12) were tested for inhibitory activity against the proliferation of human BPH-1 and human skin Hs27 fibroblast cells cultured in vitro. 1, 2 and 3 at 10 µM significantly reduced BPH-1 cell viability and were cytotoxic to Hs27 fibroblast cells. 2 was selected for further study of anti-BPH activity against testosterone induced BPH rats. At 5 mg/kg, 2 reduced the rat prostatic weight and prostatic index, consistent with the decrease in papillary acini number and epithelial thickness of the prostate tissues. These quassinoids may be potential anti-BPH compounds that require further studies.
Assuntos
Eurycoma , Hiperplasia Prostática , Quassinas , Fatores Associados à Proteína de Ligação a TATA , Masculino , Humanos , Ratos , Animais , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Eurycoma/química , Testosterona , Quassinas/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Fator de Transcrição TFIIDRESUMO
Bioactivity guided separation of Chukrasia velutina root methanolic extract led to the isolation of nine new isopimarane diterpenoids, chukranoids A-I (1-9). The absolute configuration was then assigned by comparing the experimental CD spectra and the calculated CD spectra. Chukranoids A-I (1-9) showed moderate antimalarial activity against Plasmodium falciparum 3D7 strain. It seems that conjugate system in the isopimarane skeleton may influence their antimalarial activity.
Assuntos
Antimaláricos , Diterpenos , Meliaceae , Abietanos/farmacologia , Antimaláricos/farmacologia , Diterpenos/farmacologia , Estrutura MolecularRESUMO
Bioactivity-guided separation of the methanol extract of Calophyllum scriblitifolium bark led to the isolation of five new pyranocoumarins, caloforines A-E (1-5) and two new coumarins, caloforines F and G (6 and 7). Their structures were elucidated by 1D and 2D NMR spectroscopy, and their absolute configurations were investigated by a combination of CD spectroscopy and DFT calculation. Caloforines A-F (1-6) showed moderate antimalarial activity against Plasmodium falciparum 3D7 strain.
Assuntos
Antimaláricos , Calophyllum , Piranocumarinas , Antimaláricos/farmacologia , Calophyllum/química , Cumarínicos/química , Cumarínicos/farmacologia , Casca de Planta/química , Piranocumarinas/análise , Piranocumarinas/químicaRESUMO
Eight new limonoids, walsogynes H-O (1-8) were isolated from the barks of Walsura chrysogyne, and their structures were determined on the basis of the 1D and 2D NMR data. Walsogynes H-M (1-6) and O (8) were concluded to be 11,12-seco limonoids with a dodecahydro-1H-naphtho[1,8-bc:3,4-c']difuran skeleton, and walsogyne N (7) to be 11,12-seco limonoid sharing a unique dodecahydronaphtho[1,8-bc:5,4-b'c']difuran skeleton. Walsogynes H-O (1-8) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 2.5, 2.6, 1.6, 2.5, 1.5, 2.6, 2.1, and 1.1 µM, respectively.
Assuntos
Antimaláricos , Limoninas , Meliaceae , Antimaláricos/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Plasmodium falciparumRESUMO
Cliniatines A-C (1-3), three new Amaryllidaceae alkaloids, consisting of 2,6-dimetylpyridine and lycorine-type and/or galanthamine-type were isolated from Clivia miniata (Lindl.) Bosse. The structures and absolute configurations of 1-3 were elucidated based on spectroscopic data and chemical correlation. Cliniatines A-C showed moderate inhibitory activity against acetylcholinesterase.
Assuntos
Alcaloides de Amaryllidaceae , Amaryllidaceae , Acetilcolinesterase , Alcaloides de Amaryllidaceae/farmacologia , Inibidores da Colinesterase/farmacologia , Extratos VegetaisRESUMO
Two new bisindole alkaloids, bisnaecarpamines A (1) and B (2), possessing a vobasine-sarpagine type skeleton were isolated from the bark of Tabernaemontana macrocarpa Jack. Their structures were elucidated by extensive spectroscopic methods and chemical correlation. The absolute configurations of compounds 1 and 2 were established using TDDFT-ECD calculation of the selected isomers. Bisnaecarpamine A exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 28.8 µM.
Assuntos
Alcaloides/química , Antimaláricos/química , Tabernaemontana/química , Alcaloides/farmacologia , Antimaláricos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Alcaloides Indólicos , Indonésia , Estrutura Molecular , Casca de Planta/química , Plasmodium falciparum/efeitos dos fármacosRESUMO
A novel Lycopodium alkaloid, complanadine F (1), seco-complanadine A type was isolated from the club moss Lycopodium complanatum. The planar structure and relative configuration were elucidated based on spectroscopic data.
Assuntos
Lycopodium/química , Alcaloides/química , Estrutura MolecularRESUMO
Two new bisindole alkaloids, 12'-O-demethyl-vobtusine-5-lactam and isovobtusine-N-oxide (1 and 2), were isolated from the leaves of Voacanga grandifolia, together with two known bisindole alkaloids. Their structures were elucidated on the basis of 1D and 2D NMR data. 1 and 2 showed potent antimalarial activity against Plasmodium falciparum 3D7 and very low cytotoxic activity against a human cell line, HepG2 cells.
Assuntos
Alcaloides Indólicos/química , Folhas de Planta/química , Voacanga/química , Humanos , Estrutura MolecularRESUMO
Bioactivity guided separation of Walsura trichostemon stem methanolic extract led to the isolation of four new dammarane (1-4) and two new apotirucallane triterpenoids (5-6), together with one limonoid (7), 11,25-dideacetyltrichostemonate, 12ß, 20S, 24R-trihydroxydammar-25-en-3-one and 12ß, 20S, 25-trihydroxydammar-23-en-3-one. Compounds 1-7 showed in vitro inhibitory activity on the proliferation of A549, human lung adenocarcinoma cell line.
Assuntos
Meliaceae/química , Triterpenos/química , Humanos , Estrutura Molecular , DamaranosRESUMO
The article Cycloartane triterpenoid (23R, 24E)-23-acetoxymangiferonic acid inhibited proliferation and migration in B16-F10 melanoma via MITF downregulation caused by inhibition of both ß-catenin.
RESUMO
Three new quassinoids, javanicinols A and B (1 and 2) and 4-keto-(16S)-methoxyjavanicin B (3), together with three known quassinoids (4-6) were isolated from the chloroform-soluble fraction of the methanol extract of the Picrasma javanica wood. The structures of 1-3 were determined by spectroscopic analyses, including 1D and 2D NMR, HRESIMS, and CD. The anti-HIV-1 viral protein R (Vpr) assay revealed that 1 and 2 exhibited potent anti-Vpr activities at 1.25 µM. Furthermore, the assay also revealed the potent anti-Vpr activities of (16R)-methoxyjavanicin B (7) and (16S)-methoxyjavanicin B (8), which were previously isolated from the Picrasma javanica wood.
Assuntos
Fármacos Anti-HIV/farmacologia , Produtos do Gene vpr/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Picrasma/química , Quassinas/farmacologia , Fármacos Anti-HIV/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quassinas/química , Quassinas/isolamento & purificação , Madeira/químicaRESUMO
The article Computationally-assisted discovery and structure elucidation of natural products, written by Alfarius Eko Nugroho and Hiroshi Morita, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 15 May 2019 without open access.
RESUMO
Two new sarpagine-type indole alkaloids (1 and 2), together with five known alkaloids; 12-methoxy-4-methylvoachalotine (3), 16-demethoxycarbonylvoacamine (4), isositsirikine (5), affinisine (6), affinine (7), were isolated from the bark of Tabernaemontana macrocarpa Jack. The structures of these alkaloids were determined based on spectroscopic data, chemical correlation, and comparison with the literature. 16-Demethoxycarbonylvoacamine (4) showed antiplasmodial activities against Plasmodium falciparum 3D7 and cytotoxic activities against human cell line, HepG2 cells.