RESUMO
The polyphenol oxidase (PPO) enzyme, which causes enzymatic browning, has been repeatedly purified from fruit and vegetables by affinity chromatography. In the present research, Sepharose 4B-l-tyrosine-4-amino-2-methylbenzoic acid, a novel affinity gel for the purification of the PPO enzyme with high efficiency, was synthesized. Additionally, Sepharose 4B-l-tyrosine-p-aminobenzoic acid affinity gel, known in the literature, was also synthesized, and 9.02, 16.57, and 28.13 purification folds were obtained for the PPO enzymes of potato, mushroom, and eggplant by the reference gel. The PPO enzymes of potato, mushroom, and eggplant were purified 41.17, 64.47, and 56.78-fold from the new 4-amino-2-methylbenzoic acid gel. Following their isolation from the new affinity column, the assessment of PPO enzyme purity involved the utilization of SDS-PAGE. According to the results from SDS-PAGE and native PAGE, the molecular weight of each enzyme was 50 kDa. Then, the inhibition effects of naringin, morin hydrate, esculin hydrate, homovanillic acid, vanillic acid, phloridzin dihydrate, and p-coumaric acid phenolic compounds on purified potato, mushroom, and eggplant PPO enzyme were investigated. Among the tested phenolic compounds, morin hydrate was determined to be the most potent inhibitor on the potato (Ki: 0.07 ± 0.03 µM), mushroom (Ki: 0.7 ± 0.3 µM), and eggplant (Ki: 4.8 ± 1.2 µM) PPO enzymes. The studies found that the weakest inhibitor was homovanillic acid for the potato (Ki: 1112 ± 324 µM), mushroom (Ki: 567 ± 81 µM), and eggplant (Ki: 2016.7 ± 805.6 µM) PPO enzymes. Kinetic assays indicated that morin hydrate was a remarkable inhibitor on PPO.
Assuntos
Catecol Oxidase , Cromatografia de Afinidade , Catecol Oxidase/química , Catecol Oxidase/isolamento & purificação , Catecol Oxidase/antagonistas & inibidores , Agaricales/enzimologia , Solanum tuberosum/enzimologia , Solanum tuberosum/química , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Solanum melongena/enzimologia , Solanum melongena/química , Ácidos Cumáricos/química , Propionatos/química , meta-Aminobenzoatos/química , Ácido 4-Aminobenzoico/químicaRESUMO
Natural products are a major source of new antibiotics. Here we utilize biosynthetic instructions contained within metagenome-derived congener biosynthetic gene clusters (BGCs) to guide the synthesis of improved antibiotic analogues. Albicidin and cystobactamid are the first members of a new class of broad-spectrum ρ-aminobenzoic acid (PABA)-based antibiotics. Our search for PABA-specific adenylation domain sequences in soil metagenomes revealed that BGCs in this family are common in nature. Twelve BGCs that were bio-informatically predicted to encode six new congeners were recovered from soil metagenomic libraries. Synthesis of these six predicted structures led to the identification of potent antibiotics with changes in their spectrum of activity and the ability to circumvent resistance conferred by endopeptidase cleavage enzymes.
Assuntos
Ácido 4-Aminobenzoico/síntese química , Antibacterianos/síntese química , Produtos Biológicos/síntese química , Ácido 4-Aminobenzoico/química , Antibacterianos/química , Produtos Biológicos/química , Estrutura Molecular , Compostos Orgânicos/síntese química , Compostos Orgânicos/química , Xanthomonas/químicaRESUMO
The aims of this work were to evaluate the antibacterial and antiproliferative potential in vitro of the metal complex with 4-aminobenzoic acid (Ag-pABA) and a drug delivery system based on bacterial cellulose (BC-Ag-pABA). The Ag-pABA complex was characterized by elemental analysis, high resolution mass spectrometry and single-crystal X-ray diffraction techniques, which indicated a 1:2 metal/pABA composition plus a nitrate ion coordinated to silver by the oxygen atom, with the coordination formula [Ag (C7H7NO2)2(NO3)]. The coordination of pABA to the silver ion occurred by the nitrogen atom. The in vitro antibacterial activity of the complex evaluated by minimum inhibitory concentration assays demonstrated the effective growth inhibitory activity against Gram-positive, Gram-negative biofilm producers and acid-alcohol resistant Bacillus. The antiproliferative activities against a panel of eight tumor cells demonstrated the activity of the complex with a significant selectivity index (SI). The DNA interaction capacity and the Ames Test indicated the absence of mutagenicity. The BC-Ag-pABA composite showed an effective capacity of sustained release of Ag-pABA. The observed results validate further studies on its mechanisms of action and the conditions that mediate the in vivo biological effects using animal models to confirm its safety and effectiveness for treatment of skin and soft tissues infected by bacterial pathogens, urinary tract infections and cancer.
Assuntos
Ácido 4-Aminobenzoico/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Celulose/química , Prata/farmacologia , Antibacterianos/química , Preparações de Ação Retardada , Testes de Sensibilidade Microbiana , Prata/químicaRESUMO
4-aminobenzoic acid (PABA), an essential nutrient for many human pathogens, but dispensable for humans, and its derivatives have exhibited various biological activities. In this study, we combined two pharmacophores using a molecular hybridization approach: this vitamin-like molecule and various aromatic aldehydes, including salicylaldehydes and 5-nitrofurfural, via imine bond in one-step reaction. Resulting Schiff bases were screened as potential antimicrobial and cytotoxic agents. The simple chemical modification of non-toxic PABA resulted in constitution of antibacterial activity including inhibition of methicillin-resistant Staphylococcus aureus (minimum inhibitory concentrations, MIC, from 15.62 µM), moderate antimycobacterial activity (MIC ≥ 62.5 µM) and potent broad-spectrum antifungal properties (MIC of ≥ 7.81 µM). Some of the Schiff bases also exhibited notable cytotoxicity for cancer HepG2 cell line (IC50 ≥ 15.0 µM). Regarding aldehyde used for the derivatization of PABA, it is possible to tune up the particular activities and obtain derivatives with promising bioactivities.
Assuntos
Ácido 4-Aminobenzoico/farmacologia , Antibacterianos/farmacologia , Citotoxinas/farmacologia , Ácido Fólico/química , Ácido 4-Aminobenzoico/química , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/química , Ácido Fólico/farmacologia , Células Hep G2 , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Exposure to ozone level and ultraviolet (UV) radiation is one of the major concerns in the context of public health. Numerous studies confirmed that abundant free radicals initiate undesired processes, e.g. carcinogenesis, cells degeneration, etc. Therefore, the design of redox-active molecules with novel structures, containing radical quenchers molecules with novel structures, and understanding their chemistry and biology, might be one of the prospective solutions. Methods: We designed a group of peptide dendrimers carrying multiple copies of p-aminobenzoic acid (PABA) and evaluated their molecular antioxidant properties in 1,1'-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) tests. Cytotoxicity against human melanoma and fibroblast cells as well as against primary cerebral granule cells (CGC) alone and challenged by neurotoxic sodium glutamate and production of reactive oxygen species (ROS) in presence of dendrimers were measured. Results: PABA-terminated dendrimers express enhanced radical and radical cation scavenging properties in relation to PABA alone. In cellular tests, the dendrimers at 100 M fully suppress and between 20â»100 M reduce proliferation of the human melanoma cell line. In concentration 20 M dendrimers generate small amount of the reactive oxygen species (<25%) but even in their presence human fibroblast and mouse cerebellar granule cells remain intact Moreover, dendrimers at 0.2â»20 µM concentration (except one) increased the percentage of viable fibroblasts and CGC cells treated with 100 M glutamate. Conclusions: Designed PABA-functionalized peptide dendrimers might be a potential source of new antioxidants with cationic and neutral radicals scavenging potency and/or new compounds with marked selectivity against human melanoma cell or glutamate-stressed CGC neurons. The scavenging level of dendrimers depends strongly on the chemical structure of dendrimer and the presence of other groups that may be prompted into radical form. The present studies found different biological properties for dendrimers constructed from the same chemical fragments but the differing structure of the dendrimer tree provides once again evidence that the structure of dendrimer can have a significant impact on drugâ»target interactions.
Assuntos
Ácido 4-Aminobenzoico/farmacologia , Antioxidantes/farmacologia , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Dendrímeros/farmacologia , Fibroblastos/efeitos dos fármacos , Peptídeos/farmacologia , Picratos/antagonistas & inibidores , Ácidos Sulfônicos/antagonistas & inibidores , Ácido 4-Aminobenzoico/química , Animais , Antioxidantes/síntese química , Antioxidantes/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/síntese química , Dendrímeros/química , Relação Dose-Resposta a Droga , Humanos , Camundongos , Estrutura Molecular , Peptídeos/síntese química , Peptídeos/química , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-AtividadeRESUMO
Derivatization of the natural flavonoid dihydroquercetin with p-aminobenzoic acid was carried out in an ethyl acetate/citric buffer biphasic system using laccase from the fungus Trametes hirsuta. The main reaction product yield was ~68 mol %. The product was characterized by 1H NMR, 13C NMR, and liquid chromatography-mass spectroscopy, and its structure was elucidated. The reaction product affected viability of cultured human rhabdomyosarcoma cells (RD cell line) in a dose-dependent manner and, therefore, can be of interest to pharmaceutical industry.
Assuntos
Ácido 4-Aminobenzoico/química , Biocatálise , Lacase/metabolismo , Quercetina/análogos & derivados , Acetatos/química , Linhagem Celular Tumoral , Ácido Cítrico/química , Humanos , Quercetina/química , Trametes/enzimologiaRESUMO
In this work, we report for the first time AuNPs reduced/stabilized/capped with modified para-aminobenzoic acid-quat188-pullulan (PABA-QP) as excellent nanocarriers for delivery of doxorubicin to enhance the activity and safety of these systems. Spherical AuNPs@PABA-QP obtained by facile and green synthesis under optimum conditions were characterized by UV-VIS, TEM, EDS, SAED, XRD, ATR-FTIR and zeta-potential analyses and showed a narrow size distribution of 13.7⯱â¯1.9â¯nm. DOX was successfully loaded onto AuNPs@PABA-QP via intermolecular interactions with high drug loading. DOX-AuNPs@PABA-QP (IC50â¯=â¯0.39µM) showed a 2.1-fold higher cytotoxicity against Chago cells than DOX alone (IC50â¯=â¯0.82µM), while exhibiting less cytotoxicity against normal cells (Wi-38). Moreover, DOX-AuNPs@PABA-QP also demonstrated high intracellular uptake by endocytosis, arrested in S and G2-M phases of the cell cycle (total S/G2-M increased to approximately 18.0%), induced excellent cytotoxicity, and increased the fraction of late-apoptotic cells (18.6%). Consequently, it is suggested that the novel combination of DOX-AuNPs@PABA-QP has the potential to be developed for human cancer treatment.
Assuntos
Antineoplásicos , Portadores de Fármacos , Glucanos , Ouro , Nanopartículas Metálicas , Ácido 4-Aminobenzoico/administração & dosagem , Ácido 4-Aminobenzoico/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Endocitose , Glucanos/administração & dosagem , Glucanos/química , Ouro/administração & dosagem , Ouro/química , Química Verde , Humanos , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Compostos de Amônio Quaternário/administração & dosagem , Compostos de Amônio Quaternário/químicaRESUMO
A new para-aminobenzoic-acid-containing natural product from the mango pathogenic organism Xanthomonas citri pv. mangiferaeindicae is described. By means of stable isotope precursor feeding combined with nontargeted LC-MS/MS, the generated spectra were clustered and visualized in a molecular network. This led to the identification of a new member of the meroterpenoids, termed xanthomonic acid, which is composed of an isoprenylated para-aminobenzoic acid. In vitro cytotoxicity assays demonstrated activity of xanthomonic acid against several human cancer cell lines by induction of autophagy.
Assuntos
Ácido 4-Aminobenzoico/química , Antineoplásicos/isolamento & purificação , Deutério/química , Mangifera/microbiologia , Doenças das Plantas/microbiologia , Terpenos/isolamento & purificação , Xanthomonas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Terpenos/química , Terpenos/farmacologiaRESUMO
One of the quality indicators for honey is 5-(hydroxymethyl)-2-furaldehyde (HMF), which is formed during the heating or aging of honey. The International Honey Commission recommends three methods for the determination of HMF in honey: the Winkler method, the White method, and determination by HPLC. The Winkler method uses the carcinogenic substance p-toluidine, which is not in accordance with the principles of Green Chemistry. The present work describes the determination of HMF in honey by flow injection analysis (FIA) using a modified Winkler method, replacing p-toluidine with p-aminobenzoic acid. The linear range was 1.00 to 40.0 mg L(-1), the limit of detection (LOD) was 0.43 mg L(-1), and the limit of quantification (LOQ) was 1.32 mg L(-1). The method is an efficient and environmentally friendly technique for the analysis of HMF in honey.
Assuntos
Análise de Injeção de Fluxo , Furaldeído/análogos & derivados , Mel/análise , Ácido 4-Aminobenzoico/química , Cromatografia Líquida de Alta Pressão , Furaldeído/análise , Toluidinas/químicaRESUMO
Increased usage and discharge of sunscreens have led to ecological safety crisis, and people are developing the advanced oxidation processes (AOPs) to treat them. The present study aimed to determine the degradation efficiency and mechanism of the sunscreen agent p-aminobenzoic acid (PABA) using the UV/Fe(2+)/persulphate (PS) method. A series of irradiation experiments were conducted to optimise the system conditions and to study the impacts of the natural anion. Free radicals and degradation products were identified in order to clarify the degradation mechanism. Initial PS and Fe(2+) concentrations showed significant impacts on PABA degradation. Natural anions, such as Cl(-), NO3 (-), H2PO4 (-) and HCO3 (-), impeded PABA degradation because of ion (Fe(2+)) capture, radical scavenging or pH effects. Hydroxyl (HO·) and sulphate (SO4 (·-)) radicals were two main radicals observed in the UV/Fe(2+)/PS system; of these, SO4 (·-) showed greater effects on PABA degradation. Over 99 % of the available PABA was completely degraded into carbon dioxide (CO2) and water (H2O) by the UV/Fe(2+)/PS system, and the remaining PABA participated in complex radical reactions. By-products were identified by total ion chromatography and mass spectrometry. Our research provides a treatment process for PABA with high degradation efficiency and environmental safety and introduces a new strategy for sunscreen degradation.
Assuntos
Ácido 4-Aminobenzoico/química , Protetores Solares/química , Raios Ultravioleta , Ácido 4-Aminobenzoico/efeitos da radiação , Radical Hidroxila/química , Ferro/química , Oxirredução , Sulfatos/química , Protetores Solares/efeitos da radiação , ÁguaRESUMO
PABA/NO [O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino) diazen-1-ium-1,2-diolate] is a nitric oxide (NO)-releasing arylating agent designed to be selectively activated by reaction with glutathione (GSH) on catalysis by glutathione S-transferase P1 (GSTP1), an enzyme frequently overexpressed in cancer cells. PABA/NO has proven active in several cancer models in vitro and in vivo, but its tendency to be metabolized via a variety of pathways, some that generate inactive metabolites and hydrolysis products, limits its potential as a drug. Here we show that a simple replacement of cyano for nitro at the 4 position to give compound 4b ('p-cyano-PABA/NO') has the dual effect of slowing the undesired side reactions while enhancing the proportion of NO release and arylating activity on catalysis by GSTP1. Compound 4b showed increased resistance to hydrolysis and uncatalyzed reaction with GSH, along with a more favorable product distribution in the presence of GSTP1. It also showed significant proapoptotic activity. The data suggest p-cyano-PABA/NO to be a more promising prodrug than PABA/NO, with better selectivity toward cancer cells.
Assuntos
Ácido 4-Aminobenzoico/química , Glutationa S-Transferase pi/metabolismo , Óxido Nítrico/química , Ácido 4-Aminobenzoico/metabolismo , Ácido 4-Aminobenzoico/farmacologia , Biocatálise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Glutationa/química , Glutationa/metabolismo , Glutationa S-Transferase pi/química , Células HL-60 , Humanos , Isomerismo , Cinética , Conformação Molecular , Óxido Nítrico/metabolismo , Óxido Nítrico/toxicidadeRESUMO
The year 2014 marks the centennial of events that led to the First World War ("the war to end all wars") following the assassination of Archduke Ferdinand of the crumbling Austro-Hungarian Empire. It also marks the 120th anniversary of the birth of Stephen Rothman and the 60th anniversary of the publication of his epic textbook The Physiology and Biochemistry of the Skin. In this review, we document our belief that Rothman had a seismic impact on moving investigative dermatology from a medical backwater to a scientific discipline that can hold its own with any other specialty.
Assuntos
Dermatologia/história , Fenômenos Fisiológicos da Pele , Pele/metabolismo , Ácido 4-Aminobenzoico/química , Alopecia em Áreas/terapia , Animais , Chicago , Dermatite Alérgica de Contato , Cabelo/metabolismo , História do Século XX , Humanos , Hungria , Ferro/metabolismo , Lipídeos/química , Melanócitos/citologia , Procaína/química , Progesterona/metabolismo , Glândulas Sebáceas/metabolismo , Pele/inervação , Protetores Solares/química , Sífilis/diagnóstico , Raios Ultravioleta , Urticária/terapiaRESUMO
In antioxidant activity testing, it has been argued that assays capable of measuring the inhibitive action against the biologically relevant peroxyl radicals (ROO(â¢)) from a controllable source are preferable in terms of simulating physiological conditions because ROO(â¢) is the predominant free radical found in lipid oxidation in foods and biological systems. A new fluorescent probe, p-aminobenzoic acid (PABA), was developed for selective measurement of peroxyl radical scavenging (PRS) activity of biological samples, in view of the fact that the existing PRS assays are quite laborious and require the application of strictly optimized conditions. The earlier probe, ß-phycoerythrin, of a similar PRS assay of wide use, oxygen radical absorbance capacity (ORAC), varies from lot to lot of production, undergoes photobleaching, and interacts with polyphenols via non-specific protein binding, while the current probe, fluorescein, undergoes undesired fluorescence (FL) quenching and side reactions. The developed technique is based on the fluorescence decrease of the PABA probe (within an optimal time of 30 min) because of its oxidation by ROO(â¢), generated from the thermal dissociation of 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). In the absence of the scavenger, ROO(â¢) reacted with the probe, generating non-fluorescent products, and caused a decrease in PABA fluorescence, whereas the ROO(â¢) scavenger resulted in a fluorescence increase because of the inhibition of the probe oxidation by ROO(â¢). Thus, the fluorescence increment of intact PABA is proportional to the ROO(â¢) scavenging activity of samples. The linear range of relative fluorescence intensity versus the PABA concentration was in the interval of 0.5-5.0 µM. Assay precision and accuracy were assessed by analyzing two spiked homogenates of liver and kidney at clinically relevant concentrations with 97-105% recovery and 2.3% interday reproducibility. The proposed method was successfully applied to assay the ROO(â¢) scavenging activity of some amino acids, plasma and thiol-type antioxidants, and albumin, with the latter showing the strongest activity with respect to both ORAC and developed PABA methods. On the other hand, the original ORAC method suffers a limitation from protein thiols in total radical-trapping antioxidant parameter (TRAP) calculations, and inconsistent results have been reported by various researchers for ORAC values of thiols, such as vastly differing values for glutathione and zero value for cysteine.
Assuntos
Ácido 4-Aminobenzoico/química , Corantes Fluorescentes/química , Rim/química , Fígado/química , Medições Luminescentes/métodos , Miocárdio/química , Peróxidos/análise , Animais , Medições Luminescentes/instrumentação , Masculino , Oxirredução , Ratos , Ratos WistarRESUMO
This study describes a one-pot synthesis of superparamagnetic maghemite-based 4-aminobenzoic acid-coated spherical core-shell nanoparticles (PABA@FeNPs) as suitable nanocomposites potentially usable as magnetic carriers for drug delivery. The PABA@FeNPs system was subsequently functionalized by the activated species (1* and 2*) of highly in vitro cytotoxic cis-[PtCl2(3Claza)2] (1; 3Claza stands for 3-chloro-7-azaindole) or cis-[PtCl2(5Braza)2] (2; 5Braza stands for 5-bromo-7-azaindole), which were prepared by a silver(I) ion assisted dechlorination of the parent dichlorido complexes. The products 1*@PABA@FeNPs and 2*@PABA@FeNPs, as well as an intermediate PABA@FeNPs, were characterized by a combination of various techniques, such as Mössbauer, FTIR and EDS spectroscopy, thermal analysis, SEM and TEM. The results showed that the products consist of well-dispersed maghemite-based nanoparticles of 13 nm average size that represent an easily obtainable system for delivery of highly cytotoxic cisplatin-like complexes in oncological practice.
Assuntos
Cisplatino/administração & dosagem , Portadores de Fármacos/síntese química , Sistemas de Liberação de Medicamentos , Compostos Férricos/síntese química , Ácido 4-Aminobenzoico/administração & dosagem , Ácido 4-Aminobenzoico/síntese química , Ácido 4-Aminobenzoico/química , Antineoplásicos/química , Cisplatino/química , Portadores de Fármacos/química , Compostos Férricos/química , Humanos , Indóis/síntese química , Indóis/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Prata/químicaRESUMO
Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.
Assuntos
Azepinas/química , Azepinas/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Ácido 4-Aminobenzoico/química , Ácido 4-Aminobenzoico/farmacocinética , Ácido 4-Aminobenzoico/farmacologia , Administração Oral , Adulto , Azepinas/farmacocinética , Linhagem Celular Tumoral , Descoberta de Drogas , Humanos , Inibidores de Proteínas Quinases/farmacocinética , Adulto Jovem , Quinase 1 Polo-LikeRESUMO
BACKGROUND AND AIMS: The use of vitamins including vitamin B1, B2 and K3 for the induction of systemic acquired resistance (SAR) to protect crops against plant pathogens has been evaluated previously. The use of vitamins is beneficial because it is cost effective and safe for the environment. The use of folate precursors, including ortho-aminobenzoic acid, to induce SAR against a soft-rot pathogen in tobacco has been reported previously. METHODS: In the present study, para-aminobenzoic acid (PABA, also referred to as vitamin Bx) was selected owing to its effect on the induction of SAR against Xanthomonas axonopodis pv. vesicatoria in pepper plants through greenhouse screening. KEY RESULTS: Dipping of pepper seedlings in a 1 mm PABA solution in field trials induced SAR against artificially infiltrated X. axonopodis pv. vesicatoria and naturally occurring cucumber mosaic virus. Expression of the Capsicum annuum pathogenesis-related 4 gene was primed in response to pathogen infection as assessed by quantitative real-time PCR. The accumulation of cucumber mosaic virus RNA was reduced in PABA-treated pepper plants at 40 and 105 d post-treatment. Unexpectedly, fruit yield was increased in PABA-treated plants, indicating that PABA-mediated SAR successfully protected pepper plants from infection by bacterial and viral pathogens without significant fitness allocation costs. CONCLUSIONS: The present study is the first to demonstrate the effective elicitation of SAR by a folate precursor under field conditions.
Assuntos
Ácido 4-Aminobenzoico/farmacologia , Capsicum/imunologia , Cucumovirus/fisiologia , Resistência à Doença/efeitos dos fármacos , Ácido Fólico/metabolismo , Doenças das Plantas/imunologia , Xanthomonas axonopodis/fisiologia , Ácido 4-Aminobenzoico/química , Capsicum/genética , Capsicum/microbiologia , Capsicum/virologia , Cucumovirus/efeitos dos fármacos , Resistência à Doença/genética , Resistência à Doença/imunologia , Ácido Fólico/química , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Doenças das Plantas/microbiologia , Doenças das Plantas/virologia , Transcrição Gênica/efeitos dos fármacos , Xanthomonas axonopodis/efeitos dos fármacosRESUMO
During a survey of actinobacteria known to suppress the growth of Streptomyces scabies (the causative agent of potato scab disease) in vivo, six new rhamnosylated alkaloids, the solphenazines A-F (1-6), were isolated from a biological control strain of Streptomyces (DL-93). The known rhamnosyl analogue of paraben (9) was also isolated along with a new rhamnosylated derivative of N-methyl-p-aminobenzoic acid (10). None of the compounds exhibited any antibacterial or antifungal activity against a standard panel of microorganisms, but compounds 1, 2, and 6 displayed some cytotoxicity against HCT-116 cancer cells. Additional in vitro testing provided data suggesting that the cytotoxic activity is not due to DNA intercalation or topoisomerase inhibition.
Assuntos
Antineoplásicos/isolamento & purificação , Glicosídeos/isolamento & purificação , Fenazinas/isolamento & purificação , Doenças das Plantas/microbiologia , Streptomyces , Ácido 4-Aminobenzoico/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Chlorocebus aethiops , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/farmacologia , Células HCT116 , Humanos , Rim/citologia , Rim/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenazinas/química , Fenazinas/farmacologia , Streptomyces/química , Streptomyces/efeitos dos fármacos , Streptomyces/genética , Streptomyces/crescimento & desenvolvimentoRESUMO
A series of N-acyl derivatives of 5-fluorouracil (5-FU) bearing residues of palmitic, p-myristoylaminobenzoic, p-oleoylaminobenzoic, and 1-adamantanecarbonic acids was synthesized. Relative rates of hydrolysis of derivatives mentioned under physiological conditions, at pH 7.2 and 37 degrees C, have shown that stability of these compounds increases with reducing of spatial accessibility of amide group at N1 in 5-FU. These substances incorporate easily into lipid bilayer; their liposomal preparations showed substantial cytostatic activity on HBL (human breast lymphoma) cells and are of interest as potential antitumor preparations. Also, a fluorescent analog, 1-[8-(3-perylenyl)octanoyl]-5-fluorouracil, destined for studies of the 5-FU derivatives behavior in cells and tissues was prepared.
Assuntos
Fluoruracila/administração & dosagem , Fluoruracila/química , Fluoruracila/síntese química , Ácido 4-Aminobenzoico/síntese química , Ácido 4-Aminobenzoico/química , Adamantano/análogos & derivados , Adamantano/síntese química , Adamantano/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Fluoruracila/análogos & derivados , Humanos , Hidrólise , Cinética , Lipossomos/administração & dosagem , Lipossomos/química , Ácido Palmítico/síntese química , Ácido Palmítico/químicaRESUMO
O(2)-(2,4-dinitro-5-{[2-(12-en-28-ß-D- galactopyranosyl-oleanolate-3-yl) -oxy-2-oxoethyl]amino}phenyl)1-(N-hydroxyethylmethylamino)diazen-1-ium-1,2- diolate (NG), a novel PABA/NO-based derivative of oleanolic acid (OA), has been found to show potent antitumor activity both in vivo and in vitro. In the present study, NG could significantly reduce tumor volume and weight in the H22 solid tumor mouse model. Meanwhile, NG showed selective effects on the HepG2 cells including NO generation, cytotoxic effect and apoptosis, which were prevented by hemoglobin (NO scavenger). Moreover, NG-induced apoptosis of HepG2 cells was characteristic of intracellular reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential (Δψm) and enhanced Bax-to-Bcl-2 ratio. The release of apoptotic inducing factor (AIF) and cytochrome c (Cyt c) from mitochondria and the activation of caspase-3, 9 were also detected, indicating that NG may induce apoptosis through a mitochondrial-mediated pathway. Simultaneously, NG treatment could lead to the activation of the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK but not ERK1/2. Treatment with SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38) prior to NG was found to reverse NG-induced apoptosis. Moreover, it was found that antioxidant N-acetylcysteine (NAC) blocked the induction of apoptosis and partly reversed the activation of JNK and p38, up-regulation of Bax, down-regulation of Bcl-2 and the activation of caspase-3 in NG-treated cells. Taking together, these findings suggest that NO can be released from NG, which induces apoptosis through a ROS/MAPK-mediated mitochondrial pathway.
Assuntos
Ácido 4-Aminobenzoico/química , Apoptose/efeitos dos fármacos , Compostos Azo/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Óxido Nítrico/química , Ácido Oleanólico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Ácido Oleanólico/análogos & derivados , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Prophenoloxidase (PPO) was purified from Galleria mellonella L. A 67-fold purification of the proenzyme with 352% yield was achieved by using a Sepharose 4B-L-tyrosine-p-amino benzoic acid affinity column. The purified enzyme was migrated as a single band on SDS-polyacrylamide gel electrophoresis. K(m) and V(max) values were 0.017 M and 1430.45 EU for catechol. Inhibition of PPO was investigated with inhibitors such as p-aminobenzoic acid, etyleneglycol, and ascorbic acid. Among them, ascorbic acid showed the strongest inhibitory activity with IC(50) value of 2.94 µM. The current paper represents new strategies for the biological control of the Galleria mellonella L. insect.