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Pesquisa : B01.650.940.800.575.912.250.778.188 [Categoria DeCS]
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[PMID]:28073672
[Au] Autor:Martino E; Della Volpe S; Terribile E; Benetti E; Sakaj M; Centamore A; Sala A; Collina S
[Ad] Endereço:Department of Earth and Environmental Sciences, University of Pavia, Via S. Epifanio 14, 27100 Pavia, Italy.
[Ti] Título:The long story of camptothecin: From traditional medicine to drugs.
[So] Source:Bioorg Med Chem Lett;27(4):701-707, 2017 Feb 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:20-(S)-Camptothecin (CPT) is a natural alkaloid extracted from the bark of Camptotheca acuminata (Chinese happy tree). It acts as a DNA topoisomerase 1 poison with an interesting antitumor activity and its use is limited by low stability and solubility and unpredictable drug-drug interactions. Since the late 20th century, it has been widely used in cancer therapy and, since extraction yields from plant tissues are very low, various synthetic routes have been developed to satisfy the increase in demand for CPT. Moreover, SAR studies have allowed for the development of more potent CPT analogues topotecan and irinotecan. Unfortunately, resistance has already occurred in several tumour lines. Additional studies are needed to better understand the relationship between substituents and resistance, its clinical relevance and the impact of related gene polymorphism. One of the latest research approaches focuses on modifying the delivery mode to improve tumour cell uptake and reduce toxicity.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/química
Camptotecina/análogos & derivados
Medicina Tradicional
[Mh] Termos MeSH secundário: Antineoplásicos Fitogênicos/uso terapêutico
Antineoplásicos Fitogênicos/toxicidade
Apoptose/efeitos dos fármacos
Camptotheca/química
Camptotheca/metabolismo
Camptotecina/uso terapêutico
Camptotecina/toxicidade
DNA Topoisomerases Tipo I/química
DNA Topoisomerases Tipo I/metabolismo
Seres Humanos
Neoplasias/tratamento farmacológico
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); EC 5.99.1.2 (DNA Topoisomerases, Type I); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170704
[Lr] Data última revisão:
170704
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE


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[PMID]:27584719
[Au] Autor:Li GQ; Chen NH; Zhang YB; Li P; Huang XJ; Jiang RW; Wang GC; Li YL
[Ad] Endereço:Foshan University, Foshan, 528000, P. R. China.
[Ti] Título:Six New Pentacyclic Triterpenoids from the Fruit of Camptotheca acuminata.
[So] Source:Chem Biodivers;14(1), 2017 Jan.
[Is] ISSN:1612-1880
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Six new pentacyclic triterpenoids were isolated from the fruit of Camptotheca acuminata. The chemical structures of the new compounds were elucidated by extensive spectroscopic analysis including HR-ESI-MS, IR, UV, 1D- and 2D-NMR. Moreover, the antibacterial activities of compounds 1, 2, 4, 5, and 6 were evaluated against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Dickeya zeae. All these tested compounds showed moderate antibacterial activity against Bacillus subtilis and Dickeya zeae.
[Mh] Termos MeSH primário: Antibacterianos/isolamento & purificação
Camptotheca/química
Triterpenos Pentacíclicos/isolamento & purificação
[Mh] Termos MeSH secundário: Antibacterianos/química
Antibacterianos/farmacologia
Bactérias/efeitos dos fármacos
Frutas/química
Estrutura Molecular
Triterpenos Pentacíclicos/química
Triterpenos Pentacíclicos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Pentacyclic Triterpenes)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170127
[Lr] Data última revisão:
170127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160902
[St] Status:MEDLINE
[do] DOI:10.1002/cbdv.201600180


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[PMID]:27349769
[Au] Autor:Chen F; Li W; Jiang L; Pu X; Yang Y; Zhang G; Luo Y
[Ad] Endereço:Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, People's Republic of China.
[Ti] Título:Functional characterization of a geraniol synthase-encoding gene from Camptotheca acuminata and its application in production of geraniol in Escherichia coli.
[So] Source:J Ind Microbiol Biotechnol;43(9):1281-92, 2016 Sep.
[Is] ISSN:1476-5535
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Geraniol synthase (GES) catalyzes the conversion of geranyl diphosphate (GPP) into geraniol, an acyclic monoterpene alcohol that has been widely used in many industries. Here we report the functional characterization of CaGES from Camptotheca acuminata, a camptothecin-producing plant, and its application in production of geraniol in Escherichia coli. The full-length cDNA of CaGES was obtained from overlap extension PCR amplification. The intact and N-terminus-truncated CaGESs were overexpressed in E. coli and purified to homogeneity. Recombinant CaGES showed the conversion activity from GPP to geraniol. To produce geraniol in E. coli using tCaGES, the biosynthetic precursor GPP should be supplied and transferred to the catalytic pocket of tCaGES. Thus, ispA(S80F), a mutant of farnesyl diphosphate (FPP) synthase, was prepared to produce GPP via the head-to-tail condensation of isoprenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). A slight increase of geraniol production was observed in the fermentation broth of the recombinant E. coli harboring tCaGES and ispA(S80F). To enhance the supply of IPP and DMAPP, the encoding genes involved in the whole mevalonic acid biosynthetic pathway were introduced to the E. coli harboring tCaGES and the ispA(S80F) and a significant increase of geraniol yield was observed. The geraniol production was enhanced to 5.85 ± 0.46 mg L(-1) when another copy of ispA(S80F) was introduced to the above recombinant strain. The following optimization of medium composition, fermentation time, and addition of metal ions led to the geraniol production of 48.5 ± 0.9 mg L(-1). The present study will be helpful to uncover the biosynthetic enigma of camptothecin and tCaGES will be an alternative to selectively produce geraniol in E. coli with other metabolic engineering approaches.
[Mh] Termos MeSH primário: Camptotheca/genética
Escherichia coli/genética
Monoéster Fosfórico Hidrolases/genética
Terpenos/metabolismo
[Mh] Termos MeSH secundário: Difosfatos/metabolismo
Diterpenos/metabolismo
Escherichia coli/metabolismo
Geraniltranstransferase/genética
Ácido Mevalônico/metabolismo
Monoéster Fosfórico Hidrolases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diphosphates); 0 (Diterpenes); 0 (Terpenes); 0 (geranyl diphosphate); EC 2.5.1.10 (Geranyltranstransferase); EC 3.1.3.2 (Phosphoric Monoester Hydrolases); L837108USY (geraniol); S5UOB36OCZ (Mevalonic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160629
[St] Status:MEDLINE
[do] DOI:10.1007/s10295-016-1802-2


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[PMID]:27302903
[Au] Autor:Wu D; Shi W; Zhao J; Wei Z; Chen Z; Zhao D; Lan S; Tai J; Zhong B; Yu H
[Ad] Endereço:Tumor Center of Jilin University No.1 Hospital, Changchun 130021, China.
[Ti] Título:Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205.
[So] Source:Arch Biochem Biophys;604:74-85, 2016 Aug 15.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CPT-11 (irinotecan) is a derivative of camptothecin which is a natural product derived from the Chinese tree Camptotheca acuminta and widely used in antitumor therapy. Here, the in vitro anti-tumor activity and associated mechanisms of a novel derivative of camptothecin, ZBH-1205, were investigated in a panel of 9 human tumor cell lines, as well as in HEK 293 and SK-OV-3/DPP, a multi-drug resistant (MDR) cell line, and compared to CPT-11 and 7-ethyl-10-hydroxy-camptothecin (SN38). Comparisons between the different compounds were made on the basis of IC50 values as determined by the MTT assay, and flow cytometry was used to evaluate cell cycle progression, apoptosis, and the levels of pro- and active caspase-3 among different treatment groups. Interaction between the molecules and topoisomerase-1 (Topo-1)-DNA complexes was detected by a DNA relaxation assay. Our results demonstrated that IC50 values for ZBH-1205 ranged from 0.0009 µmol/L to 2.5671 µmol/L, which were consistently lower than IC50 values of CPT-11 or SN38 in the panel of cell lines, including SK-OV-3/DPP. Furthermore, ZBH-1205 was more effective than CPT-11 or SN38 at stabilizing Topo-1-DNA complexes and inducing tumor cell apoptosis. Therefore, ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials.
[Mh] Termos MeSH primário: Antineoplásicos/química
Camptotecina/análogos & derivados
Camptotecina/química
[Mh] Termos MeSH secundário: Apoptose
Camptotheca/química
Caspase 3/metabolismo
Ciclo Celular
Linhagem Celular Tumoral
DNA/química
Ensaios de Seleção de Medicamentos Antitumorais
Células HEK293
Seres Humanos
Concentração Inibidora 50
Células K562
Cinética
Extratos Vegetais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Plant Extracts); 0 (ZBH-1205); 7673326042 (irinotecan); 9007-49-2 (DNA); EC 3.4.22.- (CASP3 protein, human); EC 3.4.22.- (Caspase 3); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160616
[St] Status:MEDLINE


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[PMID]:26609763
[Au] Autor:Guo Q; Yuan Q
[Ad] Endereço:a Department of Pharmaceutical Technology , College of Biological Engineering, Wuhan Polytechnic , Wuhan , China.
[Ti] Título:A novel 10-hydroxycamptothecin-glucoside from the fruit of Camptotheca acuminata.
[So] Source:Nat Prod Res;30(9):1053-9, 2016.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Glycosides were isolated from the fruit of Camptotheca acuminata and identified using NMR, MS, UV and IR spectrometries. 10-O-(1-ß-D-glycosyl) camptothecin (1) was identified for the first time in a natural material. In addition, compounds 2-4 were firstly reported from the fruits of C. acuminata and indentified as syringaresinol-4, 4'-O-bis-ß-D-glucoside (2), hyperoside (3) and pumiloside (4), respectively. Two known compounds, vincoside-lactam (5) and strictosidinic acid (6), were also obtained.
[Mh] Termos MeSH primário: Camptotheca/química
Camptotecina/análogos & derivados
Camptotecina/química
Frutas/química
[Mh] Termos MeSH secundário: Camptotecina/análise
Carboidratos/análise
Carbolinas/análise
Furanos/análise
Glucosídeos
Glicosídeos/análise
Hidrólise
Lignanas/análise
Espectroscopia de Ressonância Magnética
Quercetina/análogos & derivados
Quercetina/análise
Espectrometria de Massas por Ionização por Electrospray
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (10-O-(1-beta-D-glycosyl)camptothecin); 0 (Carbohydrates); 0 (Carbolines); 0 (Furans); 0 (Glucosides); 0 (Glycosides); 0 (Lignans); 0 (pumiloside); 0 (strictosidinic acid); 21453-69-0 (syringaresinol); 8O1CR18L82 (hyperoside); 9IKM0I5T1E (Quercetin); 9Z01632KRV (10-hydroxycamptothecin); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170103
[Lr] Data última revisão:
170103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151127
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2015.1107057


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[PMID]:26252645
[Au] Autor:Qu X; Pu X; Chen F; Yang Y; Yang L; Zhang G; Luo Y
[Ad] Endereço:Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, PR China; University of Chinese Academy of Sciences, Beijing, PR China.
[Ti] Título:Molecular Cloning, Heterologous Expression, and Functional Characterization of an NADPH-Cytochrome P450 Reductase Gene from Camptotheca acuminata, a Camptothecin-Producing Plant.
[So] Source:PLoS One;10(8):e0135397, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Camptothecin (CAM), a complex pentacyclic pyrroloqinoline alkaloid, is the starting material for CAM-type drugs that are well-known antitumor plant drugs. Although many chemical and biological research efforts have been performed to produce CAM, a few attempts have been made to uncover the enzymatic mechanism involved in the biosynthesis of CAM. Enzyme-catalyzed oxidoreduction reactions are ubiquitously presented in living organisms, especially in the biosynthetic pathway of most secondary metabolites such as CAM. Due to a lack of its reduction partner, most catalytic oxidation steps involved in the biosynthesis of CAM have not been established. In the present study, an NADPH-cytochrome P450 reductase (CPR) encoding gene CamCPR was cloned from Camptotheca acuminata, a CAM-producing plant. The full length of CamCPR cDNA contained an open reading frame of 2127-bp nucleotides, corresponding to 708-amino acid residues. CamCPR showed 70 ~ 85% identities to other characterized plant CPRs and it was categorized to the group II of CPRs on the basis of the results of multiple sequence alignment of the N-terminal hydrophobic regions. The intact and truncate CamCPRs with N- or C-terminal His6-tag were heterologously overexpressed in Escherichia coli. The recombinant enzymes showed NADPH-dependent reductase activity toward a chemical substrate ferricyanide and a protein substrate cytochrome c. The N-terminal His6-tagged CamCPR showed 18- ~ 30-fold reduction activity higher than the C-terminal His6-tagged CamCPR, which supported a reported conclusion, i.e., the last C-terminal tryptophan of CPRs plays an important role in the discrimination between NADPH and NADH. Co-expression of CamCPR and a P450 monooxygenase, CYP73A25, a cinnamate 4-hydroxylase from cotton, and the following catalytic formation of p-coumaric acid suggested that CamCPR transforms electrons from NADPH to the heme center of P450 to support its oxidation reaction. Quantitative real-time PCR analysis showed that CamCPR was expressed in the roots, stems, and leaves of C. acuminata seedlings. The relative transcript level of CamCPR in leaves was 2.2-fold higher than that of roots and the stems showed 1.5-fold transcript level higher than the roots. The functional characterization of CamCPR will be helpful to disclose the mysterious mechanisms of the biosynthesis of CAM. The present study established a platform to characterize the P450 enzymes involved in the growth, development, and metabolism of eukaryotic organisms.
[Mh] Termos MeSH primário: Camptotheca/genética
Camptotecina/biossíntese
NADPH-Ferri-Hemoproteína Redutase/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Antineoplásicos/química
Camptotheca/enzimologia
Catálise
Clonagem Molecular
Citocromos c/química
DNA Complementar/genética
Escherichia coli/metabolismo
Regulação da Expressão Gênica de Plantas
Modelos Moleculares
Conformação Molecular
Dados de Sequência Molecular
NADPH-Ferri-Hemoproteína Redutase/biossíntese
Fases de Leitura Aberta
Filogenia
Folhas de Planta/metabolismo
Raízes de Plantas/metabolismo
Caules de Planta/metabolismo
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/genética
Homologia de Sequência de Aminoácidos
Triptofano/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (DNA, Complementary); 0 (Recombinant Proteins); 8DUH1N11BX (Tryptophan); 9007-43-6 (Cytochromes c); EC 1.6.2.4 (NADPH-Ferrihemoprotein Reductase); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150808
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0135397


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[PMID]:26124076
[Au] Autor:Pu X; Chen F; Yang Y; Qu X; Zhang G; Luo Y
[Ad] Endereço:Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, People's Republic of China.
[Ti] Título:Isolation and characterization of Paenibacillus polymyxa LY214, a camptothecin-producing endophytic bacterium from Camptotheca acuminata.
[So] Source:J Ind Microbiol Biotechnol;42(8):1197-202, 2015 Aug.
[Is] ISSN:1476-5535
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Camptothecin (CPT) is mainly produced and extracted from Camptotheca acuminata and Nothapodytes foetida for pharmaceutical use, i.e., the starting material for chemical conversion to the clinical CPT-type drugs. As the third largest plant anticancer drug, the heavy demand on CPT from global market leads to many research efforts to identify new sources for CPT production. Herein we report the isolation and characterization of a CPT-producing endophytic bacterium Paenibacillus polymyxa LY214 from Camptotheca acuminata. A 10.7 µg l(-1) of CPT was presented in the fermentation broth of P. polymyxa LY214. Its CPT production decreased sharply when the strain of the 2nd generation of P. polymyxa LY214 was cultured and fermented. However, the CPT production remained relatively constant from 2.8 µg l(-1) of the 2nd generation to 0.8 µg l(-1) of the 8th generation of P. polymyxa LY214 under optimized fermentation conditions. A 15- to 30-fold increase of CPT yield was observed when the optimized fermentation conditions, together with the addition of putative biosynthetic precursors of CPT and adsorbent resin XAD16, were applied to ferment the strains of the 7th and 8th generation of P. polymyxa LY214. Bioinformatics analysis of the relative species of P. polymyxa LY214 indicates its potential to produce CPT, which will be helpful to decipher the mysteries of CPT biosynthesis.
[Mh] Termos MeSH primário: Camptotheca/microbiologia
Camptotecina/biossíntese
Paenibacillus/isolamento & purificação
[Mh] Termos MeSH secundário: Antineoplásicos Fitogênicos/biossíntese
Camptotheca/química
Fermentação
Magnoliopsida
Paenibacillus/genética
Paenibacillus/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150701
[St] Status:MEDLINE
[do] DOI:10.1007/s10295-015-1643-4


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[PMID]:25771119
[Au] Autor:Wang P; Luo J; Wang XB; Fan BY; Kong LY
[Ad] Endereço:State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China; School of Pharmacy, Yancheng Teachers University, Yancheng, Xiwang Road, 224051, People's Republic of China.
[Ti] Título:New indole glucosides as biosynthetic intermediates of camptothecin from the fruits of Camptotheca acuminata.
[So] Source:Fitoterapia;103:1-8, 2015 Jun.
[Is] ISSN:1873-6971
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Six new indole glucosides (1-6) and fifteen known alkaloids (7-21) were isolated from the fruit of Camptotheca acuminata. The planar structures of 1-6 were determined on the basis of spectroscopic data analysis and their absolute configurations were established by CD. The isolated indole glucosides showed a clear biosynthetic pathway of camptothecin (7), which started from tryptamine and secologanin and was proposed by synthetic chemists previously. Particularly, compound 1 supplemented the process of the transformation from pumiloside (20) or 3-epi-pumiloside (21) to camptothecin (7). In addition, camptothecin 10-O-ß-D-glucopyranoside (13) and norcamptothecin (17), synthesized in the early structural modification of 7, were first isolated from the natural resources. The new compounds 1-6 were screened for their in vitro cytotoxicity but they did not show any exciting result.
[Mh] Termos MeSH primário: Camptotheca/química
Camptotecina/biossíntese
Frutas/química
Glucosídeos/química
Indóis/química
[Mh] Termos MeSH secundário: Alcaloides/química
Alcaloides/isolamento & purificação
China
Glucosídeos/isolamento & purificação
Indóis/isolamento & purificação
Estrutura Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Alkaloids); 0 (Glucosides); 0 (Indoles); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:150603
[Lr] Data última revisão:
150603
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150316
[St] Status:MEDLINE


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[PMID]:25733498
[Au] Autor:Sirikantaramas S; Meeprasert A; Rungrotmongkol T; Fuji H; Hoshino T; Sudo H; Yamazaki M; Saito K
[Ad] Endereço:Department of Biochemistry, Faculty of Science, Chulalongkorn University, Thailand; Department of Molecular Biology and Biotechnology, Graduate School of Pharmaceutical Sciences, Chiba University, Japan. Electronic address: supaart.s@chula.ac.th.
[Ti] Título:Structural insight of DNA topoisomerases I from camptothecin-producing plants revealed by molecular dynamics simulations.
[So] Source:Phytochemistry;113:50-6, 2015 May.
[Is] ISSN:1873-3700
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:DNA topoisomerase I (Top1) catalyzes changes in DNA topology by cleaving and rejoining one strand of the double stranded (ds)DNA. Eukaryotic Top1s are the cellular target of the plant-derived anticancer indole alkaloid camptothecin (CPT), which reversibly stabilizes the Top1-dsDNA complex. However, CPT-producing plants, including Camptotheca acuminata, Ophiorrhiza pumila and Ophiorrhiza liukiuensis, are highly resistant to CPT because they possess point-mutated Top1. Here, the adaptive convergent evolution is reported between CPT production ability and mutations in their Top1, as a universal resistance mechanism found in all tested CPT-producing plants. This includes Nothapodytes nimmoniana, one of the major sources of CPT. To obtain a structural insight of the resistance mechanism, molecular dynamics simulations of CPT- resistant and -sensitive plant Top1s complexed with dsDNA and topotecan (a CPT derivative) were performed, these being compared to that for the CPT-sensitive human Top1. As a result, two mutations, Val617Gly and Asp710Gly, were identified in O. pumila Top1 and C. acuminata Top1, respectively. The substitutions at these two positions, surprisingly, are the same as those found in a CPT derivative-resistant human colon adenocarcinoma cell line. The results also demonstrated an increased linker flexibility of the CPT-resistant Top1, providing an additional explanation for the resistance mechanism found in CPT-producing plants. These mutations could reflect the long evolutionary adaptation of CPT-producing plant Top1s to confer a higher degree of resistance.
[Mh] Termos MeSH primário: Camptotheca/química
Camptotecina/biossíntese
DNA Topoisomerases Tipo I/metabolismo
Simulação de Dinâmica Molecular
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Antineoplásicos Fitogênicos/química
Antineoplásicos Fitogênicos/farmacologia
Evolução Biológica
Camptotecina/química
Camptotecina/farmacologia
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Seres Humanos
Estrutura Molecular
Mutação
Conformação Proteica
Inibidores da Topoisomerase I/química
Inibidores da Topoisomerase I/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Topoisomerase I Inhibitors); EC 5.99.1.2 (DNA Topoisomerases, Type I); EC 5.99.1.2 (TOP1 protein, human); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:150521
[Lr] Data última revisão:
150521
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150304
[St] Status:MEDLINE


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[PMID]:25728326
[Au] Autor:Li P; Chen Q; Yu F; Xie X; Wang S
[Ad] Endereço:School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China.
[Ti] Título:Simultaneous determination of camptothecin and 10-hydroxycamptothecine in the Camptotheca acuminate, its medicinal preparation and in rat plasma by liquid chromatography with fluorescence detection.
[So] Source:Biomed Chromatogr;29(10):1522-6, 2015 Oct.
[Is] ISSN:1099-0801
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Camptotheca acuminata Decne is an important medicinal plant that contains various cytotoxic alkaloids, such as camptothecine (CPT) and 10-hydroxycamptothecine (HCPT). A rapid and sensitive liquid chromatography with fluorescence detection (LC-FLD) method for the quantification of CPT and HCPT is described. The separation was carried out on a DL-Cl8 column (4.6 × 150 mm, 5 µm), with the mobile phase of acetonitrile-sodium dihydrogen phosphate buffer (10 mm) using an gradient elution at the flow rate of 0.6 mL/min. The LC-FLD method was validated for linearity, sensitivity, accuracy and precision, and then used to determine the content of the above components. The lower detection limits of CPT and HCPT were 0.4 and 0.1 ng/mL, respectively. The precision was <1.58% and the mean recovery of the analytes was 96.0-98.6%. The LC-FLD method was successfully applied to determine CPT and HCPT in real samples including C. acuminate, HCPT injection and rat plasma.
[Mh] Termos MeSH primário: Camptotheca/química
Camptotecina/análogos & derivados
Camptotecina/análise
Cromatografia Líquida/métodos
[Mh] Termos MeSH secundário: Administração Oral
Animais
Camptotecina/administração & dosagem
Camptotecina/sangue
Cromatografia Líquida/instrumentação
Medicamentos de Ervas Chinesas/análise
Medicamentos de Ervas Chinesas/química
Fluorescência
Limite de Detecção
Plantas Medicinais/química
Ratos Sprague-Dawley
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Drugs, Chinese Herbal); 9Z01632KRV (10-hydroxycamptothecin); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150303
[St] Status:MEDLINE
[do] DOI:10.1002/bmc.3452



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