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1.
Bioorg Med Chem Lett ; 40: 127967, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33753259

RESUMO

An ethanolic extract of Derris scandens flowers showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived condition, with a PC50 value of 0.7 µg/mL. Phytochemical investigation of this active extract led to the isolation of four prenylated isoflavones (1-4) including a new compound named 4'-O-methylgrynullarin (1). The structure elucidation of the new compound was achieved by HRFABMS and NMR spectroscopic analysis. The isolated compounds exhibited potent anti-austerity activity against four different human pancreatic cancer cell lines under nutrient-deprived conditions. The new compound 4'-O-methylgrynullarin (1) was also found to inhibit PANC-1 cell migration and colony formation under nutrient-rich condition. Mechanistically, compound 1 inhibited key survival proteins in the Akt/mTOR signaling pathway. Therefore, 4'-O-methylgrynullarin (1) can be considered as a potential lead compound for the anticancer drug development based on the anti-austerity strategy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Morte Celular/efeitos dos fármacos , Hemiterpenos/farmacologia , Isoflavonas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Derris/química , Ensaios de Seleção de Medicamentos Antitumorais , Flores/química , Hemiterpenos/síntese química , Hemiterpenos/isolamento & purificação , Humanos , Isoflavonas/química , Isoflavonas/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
2.
Bioorg Chem ; 107: 104529, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33339665

RESUMO

In our screening program for new biologically active secondary metabolites, nine new polycyclic polyprenyled acylphloroglucinols, hyperscabins D-L, together with three known compounds, were obtained from the aerial parts of Hypericum scabrum. The chemical structures of 1-9 were characterized by extensive spectroscopic analyses, nuclear magnetic resonance calculation with DP4+ probability analysis, and the electronic circular dichroism spectra were calculated. Compound 1 was an unusual prenylated acylphloroglucinol decorated with a 5-oxaspiro [4,5] deca-1,9-dione skeleton. Compound 2 was a newly identified spirocyclic polyprenylated acylphloroglucinol possessing a rare 5,5-spiroketal segment. Compounds 3, 8, and 10 (10 µM) exhibited pronounced hepatoprotective activity against d-galactosamine-induced WB-F344 cell damage in vitro assays. All test compounds (1, 3, and 7-12) demonstrated potential inhibitory effects at 10 µM against noradrenalinet ([3H]-NE) reuptake in rat brain synaptosome.


Assuntos
Antidepressivos/farmacologia , Hemiterpenos/farmacologia , Hypericum/química , Floroglucinol/análogos & derivados , Floroglucinol/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antidepressivos/síntese química , Antidepressivos/isolamento & purificação , Linhagem Celular , Hemiterpenos/síntese química , Hemiterpenos/isolamento & purificação , Inibidores da Captação de Neurotransmissores/síntese química , Inibidores da Captação de Neurotransmissores/isolamento & purificação , Inibidores da Captação de Neurotransmissores/farmacologia , Norepinefrina/metabolismo , Floroglucinol/isolamento & purificação , Componentes Aéreos da Planta/química , Substâncias Protetoras/síntese química , Substâncias Protetoras/isolamento & purificação , Ratos , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
3.
BMC Plant Biol ; 20(1): 167, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293285

RESUMO

BACKGROUND: Deoxyxylulose 5-phosphate synthase (DXS) and deoxyxylulose 5-phosphate reductoisomerase (DXR) are the enzymes that catalyze the first two enzyme steps of the methylerythritol 4-phosphate (MEP) pathway to supply the isoprene building-blocks of carotenoids. Plant DXR and DXS enzymes have been reported to function differently depending on the plant species. In this study, the differential roles of rice DXS and DXR genes in carotenoid metabolism were investigated. RESULTS: The accumulation of carotenoids in rice seeds co-expressing OsDXS2 and stPAC was largely enhanced by 3.4-fold relative to the stPAC seeds and 315.3-fold relative to non-transgenic (NT) seeds, while the overexpression of each OsDXS2 or OsDXR caused no positive effect on the accumulation of either carotenoids or chlorophylls in leaves and seeds, suggesting that OsDXS2 functions as a rate-limiting enzyme supplying IPP/DMAPPs to seed carotenoid metabolism, but OsDXR doesn't in either leaves or seeds. The expressions of OsDXS1, OsPSY1, OsPSY2, and OsBCH2 genes were upregulated regardless of the reductions of chlorophylls and carotenoids in leaves; however, there was no significant change in the expression of most carotenogenic genes, even though there was a 315.3-fold increase in the amount of carotenoid in rice seeds. These non-proportional expression patterns in leaves and seeds suggest that those metabolic changes of carotenoids were associated with overexpression of the OsDXS2, OsDXR and stPAC transgenes, and the capacities of the intermediate biosynthetic enzymes might be much more important for those metabolic alterations than the transcript levels of intermediate biosynthetic genes are. Taken together, we propose a 'Three Faucets and Cisterns Model' about the relationship among the rate-limiting enzymes OsDXSs, OsPSYs, and OsBCHs as a "Faucet", the biosynthetic capacity of intermediate metabolites as a "Cistern", and the carotenoid accumulations as the content of "Cistern". CONCLUSION: Our study suggests that OsDXS2 plays an important role as a rate-limiting enzyme supplying IPP/DMAPPs to the seed-carotenoid accumulation, and rice seed carotenoid metabolism could be largely enhanced without any significant transcriptional alteration of carotenogenic genes. Finally, the "Three Faucets and Cisterns model" presents the extenuating circumstance to elucidate rice seed carotenoid metabolism.


Assuntos
Aldose-Cetose Isomerases/fisiologia , Carotenoides/metabolismo , Eritritol/análogos & derivados , Oryza/enzimologia , Fosfatos Açúcares/fisiologia , Aldose-Cetose Isomerases/genética , Butadienos/síntese química , Butadienos/metabolismo , Eritritol/genética , Eritritol/fisiologia , Hemiterpenos/síntese química , Hemiterpenos/metabolismo , Folhas de Planta/enzimologia , Sementes/enzimologia , Fosfatos Açúcares/genética , Transferases/genética , Transferases/fisiologia
4.
Chemistry ; 26(10): 2178-2182, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31898827

RESUMO

Methylated analogues of isopentenyl diphosphate were synthesised and enzymatically incorporated into methylated terpenes. A detailed stereochemical analysis of the obtained products is presented. The methylated terpene precursors were also used in conjunction with various isotopic labellings to gain insights into the mechanisms of their enzymatic formation.


Assuntos
Alquil e Aril Transferases/metabolismo , Bactérias/enzimologia , Proteínas de Bactérias/metabolismo , Terpenos/metabolismo , Chloroflexi/enzimologia , Chryseobacterium/enzimologia , Hemiterpenos/síntese química , Hemiterpenos/química , Hemiterpenos/metabolismo , Metilação , Compostos Organofosforados/síntese química , Compostos Organofosforados/química , Compostos Organofosforados/metabolismo , Estereoisomerismo , Terpenos/química
5.
Chembiochem ; 20(17): 2217-2221, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-30998839

RESUMO

Isoprenoids are a large class of natural products with wide-ranging applications. Synthetic biology approaches to the manufacture of isoprenoids and their new-to-nature derivatives are limited due to the provision in nature of just two hemiterpene building blocks for isoprenoid biosynthesis. To address this limitation, artificial chemo-enzymatic pathways such as the alcohol-dependent hemiterpene (ADH) pathway serve to leverage consecutive kinases to convert exogenous alcohols into pyrophosphates that could be coupled to downstream isoprenoid biosynthesis. To be successful, each kinase in this pathway should be permissive of a broad range of substrates. For the first time, we have probed the promiscuity of the second enzyme in the ADH pathway-isopentenyl phosphate kinase from Thermoplasma acidophilum-towards a broad range of acceptor monophosphates. Subsequently, we evaluate the suitability of this enzyme to provide unnatural pyrophosphates and provide a critical first step in characterizing the rate-limiting steps in the artificial ADH pathway.


Assuntos
Hemiterpenos/síntese química , Proteínas Quinases/metabolismo , Especificidade por Substrato , Terpenos/síntese química , Thermoplasma/enzimologia , Álcoois , Difosfatos/metabolismo , Fosfatos/metabolismo , Biologia Sintética/métodos
6.
J Am Chem Soc ; 140(47): 16020-16025, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30424602

RESUMO

The prenyl fragment is the quintessential constituent of terpenoid natural products, a diverse family which contains numerous members with diverse biological properties. In contrast, fluorinated and multifluorinated arenes make up an important class of anthropogenic molecules which are highly relevant to material, agricultural, and pharmaceutical industries. While allylation chemistry is well developed, effective prenylation strategies have been less forthcoming. Herein, we describe the photocatalytic defluoroprenylation, a powerful method that provides access to "hybrid molecules" that possess both the functionality of a prenyl group and fluorinated arenes. This approach involves direct prenyl group transfer under very mild conditions, displays excellent functional group tolerance, and includes relatively short reaction times (<4 h), which is the fastest photocatalytic C-F functionalization developed to date. Additionally, the strategy can be extended to include allyl and geranyl (10 carbon fragment) transfers. Another prominent finding is a reagent-dependent switch in regioselectivity of the major product from para to ortho C-F functionalization.


Assuntos
Fluorbenzenos/química , Hemiterpenos/química , Catálise/efeitos da radiação , Técnicas de Química Sintética/métodos , Complexos de Coordenação/química , Complexos de Coordenação/efeitos da radiação , Fluorbenzenos/síntese química , Radicais Livres/química , Hemiterpenos/síntese química , Irídio/química , Luz , Estrutura Molecular , Prenilação/efeitos da radiação
7.
Macromol Rapid Commun ; 39(9): e1800043, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29578265

RESUMO

The synthesis and self-assembly in thin-film configuration of linear ABC triblock terpolymer chains consisting of polystyrene (PS), poly(2-vinylpyridine) (P2VP), and polyisoprene (PI) are described. For that purpose, a hydroxyl-terminated PS-b-P2VP (45 kg mol-1 ) building block and a carboxyl-terminated PI (9 kg mol-1 ) are first separately prepared by anionic polymerization, and then are coupled via a Steglich esterification reaction. This quantitative and metal-free catalyst synthesis route reveals to be very interesting since functionalization and purification steps are straightforward, and well-defined terpolymers are produced. A solvent vapor annealing (SVA) process is used to promote the self-assembly of frustrated PS-b-P2VP-b-PI chains into a thin-film core-shell double gyroid (Q230 , space group: Ia3¯d) structure. As terraces are formed within PS-b-P2VP-b-PI thin films during the SVA process under a CHCl3 vapor, different plane orientations of the Q230 structure ((211), (110), (111), and (100)) are observed at the polymer-air interface depending on the film thickness.


Assuntos
Butadienos/química , Hemiterpenos/química , Nanoestruturas/química , Pentanos/química , Poliestirenos/química , Polivinil/química , Butadienos/síntese química , Hemiterpenos/síntese química , Tamanho da Partícula , Pentanos/síntese química , Polímeros/síntese química , Polímeros/química , Poliestirenos/síntese química , Polivinil/síntese química
8.
J Endod ; 40(10): 1658-62, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25260740

RESUMO

INTRODUCTION: Pure gutta-percha (trans-1, 4-polyisoprene [TPI]) has been used extensively as a main component of gutta-percha for root canal filling. TPI has the interesting shape memory property by cross-linking, and this polymer was commercialized under the product name of SMP-2 (Kuraray Corp, Kashima, Japan). Therefore, the purpose of this study was to examine the thermal properties and the mechanism of the shape memory function of cross-linked SMP-2. METHODS: The crystalline of the TPI was observed by x-ray diffraction. The effects of temperature on shape recovery, recovery stress, and relaxation modulus (Er[5]) were measured in cross-linked cylindrical specimens of SMP-2. Differential scanning calorimetry was used to monitor thermal events. RESULTS: On heating, a pronounced increase in recovery stress, a marked decrease in Er(5), and endothermic DSC peaks were observed over the same temperature range (38°-51°C) with shape recovery. On the other hand, on cooling, a pronounced decrease in recovery stress, a marked increase in Er(5), and an exothermic DSC peak were observed over the same temperature range (27°-33°C). CONCLUSIONS: The shape memory property of TPI is derived from its crystallinity and cross-linking ability. Fixing the deformed shape and shape recovery from the deformed shape to the original shape is relatively easy to achieve by changing the temperature of SMP-2. The shape memory function of the cross-linked SMP-2 was expected to be very useful as a root canal filling material by the modification of its some thermal properties.


Assuntos
Hemiterpenos/química , Látex/química , Polímeros/química , Benzotiazóis/química , Carbonato de Cálcio/química , Varredura Diferencial de Calorimetria/métodos , Reagentes de Ligações Cruzadas/química , Cristalografia/métodos , Módulo de Elasticidade , Hemiterpenos/síntese química , Humanos , Látex/síntese química , Teste de Materiais , Fenóis/química , Polímeros/síntese química , Materiais Restauradores do Canal Radicular/química , Ácidos Esteáricos/química , Estresse Mecânico , Enxofre/química , Propriedades de Superfície , Temperatura , Tiram/química , Titânio/química , Difração de Raios X/métodos , Óxido de Zinco/química
9.
Dalton Trans ; 42(25): 9033-9, 2013 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-23571673

RESUMO

The synthesis and structural characterisation of the uranium(IV) amido-borohydrides (N'')2U{κ(2)-N(SiMe3)SiMe2CH2BBN-H} and U{κ(2)-N(SiMe3)SiMe2CH2BBN-H}2, and their activity as pre-catalysts for the polymerisation of isoprene are described.


Assuntos
Amidas/química , Boroidretos/química , Butadienos/química , Hemiterpenos/química , Hemiterpenos/síntese química , Látex/síntese química , Compostos Organometálicos/química , Pentanos/química , Urânio/química , Catálise , Látex/química , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Polimerização
10.
Chem Asian J ; 7(1): 143-55, 2012 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-22034218

RESUMO

The novel double-stage convergent synthesis of a new class of polyisoprene terpenoid (PIPTP) dendrons is described. PIPTP dendrons bear a highly branched aliphatic hydrocarbon skeleton and a hydrophilic hydroxy focal point functionality. These dendrons have the specific formula C((5×2)(G+1)(-5))H((5×2)(G+2)(-8))O, and each dendritic layer is constructed from an isoprene unit. The key branching steps involve a double alkyl-metal addition to an ester functionality, followed by deoxygenation of the resulting tertiary alcohol by triethylsilane and trifluoroacetic acid, then hydrogenation or hydrogenolysis. The dendrons were also attached to oligo(phenylene ethynylene)s (OPEs) so as to function as protective shells to allow fine tuning of the nanoscopic environment around the OPE moiety, and to exert precise control of the packing density and intermolecular interaction between the OPE cores. Fluorescence quantum yield data reveal that the OPE core is better encapsulated by the PIPTP dendrons than by Fréchet dendrons.


Assuntos
Alcinos/síntese química , Dendrímeros/síntese química , Éteres/síntese química , Hemiterpenos/síntese química , Látex/síntese química , Terpenos/síntese química , Alcinos/química , Dendrímeros/química , Éteres/química , Hemiterpenos/química , Látex/química , Estrutura Molecular , Terpenos/química
12.
J Med Chem ; 54(13): 4918-22, 2011 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-21618996

RESUMO

Vitamin K(2) has been demonstrated to induce gene expression related to bone formation through a nuclear steroid and xenobiotic receptor (SXR). We synthesized new vitamin K analogues with the same isoprene side chains symmetrically introduced at the 2 and 3 positions of 1,4-naphthoquinone and evaluated the transcriptional activity of the target gene. The transcriptional activity was related to the length of the side chain which allowed optimal interaction with ligand-binding domain of SXR.


Assuntos
Receptores de Esteroides/agonistas , Vitamina K/análogos & derivados , Vitamina K/síntese química , Sítios de Ligação , Butadienos/síntese química , Butadienos/química , Butadienos/farmacologia , Genes Reporter , Hemiterpenos/síntese química , Hemiterpenos/química , Hemiterpenos/farmacologia , Células Hep G2 , Humanos , Ligantes , Luciferases/biossíntese , Luciferases/genética , Pentanos/síntese química , Pentanos/química , Pentanos/farmacologia , Receptor de Pregnano X , Receptores de Esteroides/genética , Relação Estrutura-Atividade , Transcrição Gênica/efeitos dos fármacos , Vitamina K/farmacologia
13.
J Org Chem ; 76(6): 1838-43, 2011 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-21344952

RESUMO

Substrate analogues for isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), where the C3 methyl groups were replaced by chlorine, were synthesized and evaluated as substrates for avian farnesyl diphosphate synthase (FPPase). The IPP analogue (3-ClIPP) was a cosubstrate when incubated with dimethylallyl diphosphate (DMAPP) or geranyl diphosphate (GPP) to give the corresponding chlorinated analogues of geranyl diphosphate (3-ClGPP) and farnesyl diphosphate (3-ClFPP), respectively. No products were detected in incubations of 3-ClIPP with 3-ClDMAPP. Incubation of IPP with 3-ClDMAPP gave 11-ClFPP as the sole product. Values of K(M)(3-ClIPP) (with DMAPP) and K(M)(3-ClDMAPP) (with IPP) were similar to those for IPP and DMAPP; however, values of k(cat) for both analogues were substantially lower. These results are consistent with a dissociative electrophilic alkylation mechanism where the rate-limiting step changes from heterolytic cleavage of the carbon-oxygen bond in the allylic substrate to alkylation of the double bond of the homoallylic substrate.


Assuntos
Geraniltranstransferase/metabolismo , Halogenação , Hemiterpenos/síntese química , Hemiterpenos/metabolismo , Compostos Organofosforados/síntese química , Compostos Organofosforados/metabolismo , Animais , Geraniltranstransferase/química , Hemiterpenos/química , Cinética , Modelos Moleculares , Compostos Organofosforados/química , Conformação Proteica
14.
J Am Chem Soc ; 132(39): 13642-4, 2010 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-20831187

RESUMO

The asymmetric total synthesis of the polyprenylated acylphloroglucinol hyperibone K has been achieved using an enantioselective alkylative dearomatization-annulation process. NMR and computational studies were employed to probe the mode of action of a chiral phase-transfer (ion pair) catalyst.


Assuntos
Adamantano/análogos & derivados , Hemiterpenos/síntese química , Floroglucinol/análogos & derivados , Floroglucinol/síntese química , Adamantano/síntese química , Adamantano/química , Alquilação , Catálise , Cristalografia por Raios X , Hemiterpenos/química , Modelos Moleculares , Estrutura Molecular , Floroglucinol/química , Estereoisomerismo
15.
Bioorg Med Chem Lett ; 19(18): 5419-22, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19679472

RESUMO

In this study, we synthesized some natural and semi-synthetic prenyloxyphenylpropanoids (e.g., acetophenones, benzoic and cinnamic acids, chalcones, and coumarins), and we assessed their in vivo neuroprotective activity, using the mouse maximal electroshock-induced seizure model (MES test). 7-Isopentenyloxycoumarin and (2E)-3-{4-[(3-methylbut-2-enyl)oxy]phenyl}prop-2-enoic acid, administered ip at a dose of 300 mg/kg, suppressed MES-induced seizures in mice in a time- and dose-dependent manner.


Assuntos
Anticonvulsivantes/síntese química , Anticonvulsivantes/uso terapêutico , Hemiterpenos/síntese química , Hemiterpenos/uso terapêutico , Éteres Fenílicos/síntese química , Éteres Fenílicos/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/química , Relação Dose-Resposta a Droga , Eletrochoque , Hemiterpenos/química , Camundongos , Éteres Fenílicos/química
16.
J Med Chem ; 52(12): 3716-22, 2009 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-19453173

RESUMO

The Vgamma9 Vdelta2 T cells mediate rapid, innate-like immune responses to pathogens and are important in several key immunoregulatory pathways, including those involved in infections and tumor development. Vgamma9 Vdelta2 T cells respond to low molecular weight isoprenoid phosphoantigens; the prototypic stimulatory compound is isopentenylpyrophosphate (IPP), an alkylphosphate intermediate of mevalonate metabolism that elicits proliferative, cytotoxic, and cytokine secretion responses. We studied the replacement of the pyrophosphate moiety with the thiopyrophosphate bioisostere, synthesizing thioanalogues of IPP and 4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP, the most potent natural antigen known to date). Once their in vitro efficacy and stability had been demonstrated, we synthesized a small library of compounds through the development of an innovative solid-phase strategy. Biological results confirmed thioHMBPP to be the best compound of this first series. Future aims are (i) the exploitation of the parallel solid-phase strategy to further explore structure-activity relationships of this new class of synthetic antigens and (ii) the determination of the PK/PD profile of thioHMBPP.


Assuntos
Hemiterpenos/síntese química , Hemiterpenos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Compostos Organofosforados/síntese química , Compostos Organofosforados/farmacologia , Receptores de Antígenos de Linfócitos T gama-delta/efeitos dos fármacos , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Hemiterpenos/química , Ativação Linfocitária/imunologia , Estrutura Molecular , Peso Molecular , Compostos Organofosforados/química , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Bibliotecas de Moléculas Pequenas , Estereoisomerismo , Relação Estrutura-Atividade , Compostos de Sulfidrila/química
17.
Macromol Biosci ; 8(8): 711-27, 2008 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-18504805

RESUMO

Fluorescent polyisoprene nanoparticles were synthesized by the miniemulsion technique as marker particles for cells. The uptake of the non-functionalized polyisoprene nanoparticles, without any transfection agents, into different adherent (HeLa) and also suspension (Jurkat) cell lines is strikingly efficient and fast compared to other polymeric particles, and leads to high loading of the cells. The intracellular polyisoprene particles are localized as single particles in endosomes distributed throughout the entire cytoplasm. The uptake kinetics shows that particle internalization starts during the first minutes of incubation and is finished after 48 h of incubation. Since (unfunctionalized) polystyrene particles show a comparable, low uptake behavior in cells, the uptake rates can be tuned by the amount of polystyrene in polyisoprene/polystyrene copolymer particles. As polyisoprene nanoparticles are internalized by different cell lines that are relevant for biomedical applications, they can be used to label these cells efficiently if a marker is incorporated in the particles. As polyisoprene is not or is hardly biodegradable the particles should be suited for long-term applications.


Assuntos
Butadienos/síntese química , Butadienos/farmacologia , Endossomos/ultraestrutura , Corantes Fluorescentes/síntese química , Hemiterpenos/síntese química , Hemiterpenos/farmacologia , Nanopartículas , Pentanos/síntese química , Pentanos/farmacologia , Poliestirenos/síntese química , Poliestirenos/farmacologia , Butadienos/química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Células HeLa , Hemiterpenos/química , Humanos , Células Jurkat , Cinética , Nanopartículas/química , Pentanos/química , Poliestirenos/química , Fatores de Tempo
19.
Bioorg Med Chem ; 14(16): 5721-8, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16697207

RESUMO

We designed and synthesized isoprene analogues of artepillin C, a major component of Brazilian propolis, and investigated the inhibitory activity on lipid peroxidation of rat liver mitochondria (RLM) and RLM toxicity based on isoprenomics. We succeeded in the synthesis of artepillin C isoprene analogues using regioselective prenylation within the range from 22% to 53% total yield. Reactivity of artepillin C and its isoprene analogues with ABTS (2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonate)) radical cations showed only a slight difference among the molecules. The isoprene side-chain elongation analogues of artepillin C showed almost the same inhibitory activity against RLM lipid peroxidation as artepillin C. Artepillin C and its isoprene analogues had very weak RLM uncoupling activity. Moreover, artepillin C and its isoprene analogues exhibited a lower inhibitory activity against adenosine 5'-triphosphate (ATP) synthesis by about two orders of magnitude than the effective inhibitory activity against RLM lipid peroxidation. From these results we conclude that artepillin C isoprene analogues could be potent lipid peroxidation inhibitors having low mitochondrial toxicity. We also conclude that elongation of the isoprene side chain of artepillin C to increase lipophilicity had little influence on the inhibitory activity toward RLM lipid peroxidation.


Assuntos
Butadienos/farmacologia , Ácidos Graxos/farmacologia , Hemiterpenos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Pentanos/farmacologia , Fenilpropionatos/farmacologia , Trifosfato de Adenosina/biossíntese , Animais , Butadienos/síntese química , Desenho de Fármacos , Ácidos Graxos/síntese química , Hemiterpenos/síntese química , Masculino , Modelos Químicos , Pentanos/síntese química , Fenilpropionatos/síntese química , Ratos , Ratos Wistar
20.
J Org Chem ; 71(4): 1739-41, 2006 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-16468838

RESUMO

Short practical syntheses for five deuterium-labeled derivatives of dimethylallyl diphosphate (DMAPP) useful for enzymological studies are reported. These include the preparation of the C1-labeled derivatives (R)-[1-2H]3-methylbut-2-enyl diphosphate ((R)-[1-2H]1-OPP) and (S)-[1-2H]3-methylbut-2-enyl diphosphate ((S)-[1-2H]1-OPP), the C2-labeled derivative [2-2H]3-methylbut-2-enyl diphosphate ([2-2H]1-OPP), and the methyl-labeled derivatives (E)-[4,4,4-2H3]3-methylbut-2-enyl diphosphate ((E)-[4,4,4-2H3]1-OPP) and (Z)-[4,4,4-2H3]3-methyl-but-2-enyl diphosphate ((Z)-[4,4,4-2H3]1-OPP).


Assuntos
Deutério , Hemiterpenos/síntese química , Marcação por Isótopo/métodos , Compostos Organofosforados/síntese química , Enzimas/metabolismo
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