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1.
Exploring novel chemotherapeutic agents is a great challenge in cancer medicine. To that end, 2-substituted benzimidazole copper(II) complex, [Cu(BMA)Cl2]·(CH3OH) (1) [BMA = N,N′-bis(benzimidazol-2-yl-methyl)amine], was synthesized and its cytotoxicity was characterized. The interaction between complex 1 and calf thymus DNA was detected by spectroscopy methods. The binding constant (K b = 1.24 × 10M?1) and the apparent binding constant (K app = 6.67 × 10M?1) of 1 indicated its moderate DNA affinity. Complex 1 induced single strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. Cytotoxicity studies proved that complex 1 could inhibit the proliferation of human cervical carcinoma cell line HeLa in both time- and dose-dependent manners. The results of nuclei staining by Hoechst 33342 and alkaline single-cell gel electrophoresis proved that complex 1 caused cellular DNA damage in HeLa cells. Furthermore, treatment of HeLa cells with 1 resulted in S-phase arrest, loss of mitochondrial potential, and up-regulation of caspase-3 and -9 in HeLa cells, suggesting that complex 1 was capable of inducing apoptosis in cancer cells through the intrinsic mitochondrial pathway.  相似文献   

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A novel series of naphthalimide polyamine conjugates were designed, synthesized and evaluated for in vitro antiproliferative activity against human leukemia (Jurkat), human cervical adenocarcinoma (HeLa), human breast adenocarcinoma (MCF-7) and human lung adenocarcinoma (A549) cell lines. From the six derivatives, the new I1 and A3 exhibited highest antiproliferative activity with the IC50 values of 5.67–11.02 μmol·L?1. Cell cycle analysis of Jurkat cells exposed to I1 at a concentration of 30 μmol × L?1 for 24 h exhibited a mild increase in S and G2/M fraction caused by accumulation of cells. This arrest was followed by an increase in sub-G0/G1 after 48 h of incubation. Jurkat cells exposed to A3 at a concentration of 30 μmol × L?1 for 24 h showed an increase in G0/G1 fraction and after 48 h an increase in G2/M fraction followed by an increase in sub-G0/G1 after 72 h of incubation. Moreover, the A3 compound was observed to displace the intercalating agent ethidium bromide from calf thymus DNA using fluorescence spectroscopy. The apparent binding constant was estimated to be 3.1 × 106 M?1 what indicates non-intercalating mode of DNA binding. On the other hand, we found no inhibitory effect of studied compounds on topoisomerase I and topoisomerase II activity. Finally, the localization of these compounds in the cells due to their inherent fluorescence was investigated with the fluorescence microscopy. Our results suggest that the naphthalimide polyamine conjugates rapidly penetrate to the cancer cells. Further studies are necessary to investigate the precise mechanism of action and to find out the relationship between the structure, character and position of substituents of naphthalimide polyamine conjugates and their biological activities.  相似文献   

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The compounds terrein (1), butyrolactone I (2), and butyrolactone V (3) were isolated from the ethyl acetate extract (EtOAc) of the endophytic fungus Aspergillus terreus—F7 obtained from Hyptis suaveolens (L.) Poit. The extract and the compounds presented schistosomicidal activity against Schistosoma mansoni; at 100 µg/mL for EtOAc extract, 1297.3 µM for compound 1, 235.6 µM for compound 2, and 454.1 µM for compound 3, they killed 100% of the parasites after 72 h of treatment. Compounds 1, 2, and 3 exerted moderate leishmanicidal activity against Leishmania amazonensis (IC50 ranged from 23.7 to 78.6 µM). At 235.6 and 227.0 µM, compounds 2 and 3, respectively, scavenged 95.92 and 95.12% of the DPPH radical (2,2-diphenyl-1-picryl-hydrazyl), respectively. Regarding the cytotoxicity against the breast tumor cell lines MDA-MB-231 and MCF-7, compound 2 gave IC50 of 34.4 and 17.4 µM, respectively, while compound 3 afforded IC50 of 22.2 and 31.9 µM, respectively. At 117.6 µM, compound 2 inhibited the growth of and killed the pathogen Escherichia coli (ATCC 25922). Compounds 1, 2, and 3 displayed low toxicity against the normal line of human lung fibroblasts (GM07492A cells), with IC50 of 15.3?×?103, 3.4?×?103, and 5.8?×?103 µM, respectively. This is the first report on (i) the in vitro schistosomicidal and leishmanicidal activities of the EtOAc extract of A. terreus—F7 and compounds 1, 2, and 3; and (ii) the antitumor activity of compounds 2 and 3 against MDA-MB-231 and MCF-7 cells.  相似文献   

6.
Four new platinum(II) complexes: PtII L1·H2O (C1, H2 L1 = C20H16N2O2), PtII L2Cl2 (C2, L2 = C22H16N2O2), PtII L3Cl2·H2O (C3, L3 = C20H16N2), PtII L4Cl2·0.4H2O (C4, L4 = C18H14N4) have been synthesized and characterized by using various physico-chemical techniques. The binding interaction of the four platinum(II) complexes C1C4 with calf thymus (CT)-DNA has been investigated by UV–Vis and fluorescence emission spectrometry. The apparent binding constant (K app) values follow the order: C3 > C1 > C2 > C4. In addition, fluorescence spectrometry of bovine serum albumin (BSA) with the four platinum(II) complexes C1C4 showed that the quenching mechanism might be a static quenching procedure. For C1C4, the number of binding sites was about one for BSA and the binding constants follow the order: C3 (7.08 × 105M?1) > C1 (2.82 × 105M?1) > C2 (0.85 × 105M?1) > C4 (0.15 × 105M?1). With the single condition change such as absence of an external agent, the DNA cleavage abilities of C3 exhibit remarkable changes. In addition, the cytotoxicity of C3 in vitro on tumor cells lines (MCF-7, HepG2 and HT29) were examined by MTT and showed better antitumor effects on the tested cells.  相似文献   

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Thiosemicarbazones have become one of the promising compounds as new clinical candidates due to their wide spectrum of pharmaceutical activities. The wide range of their biological activities depends generally on their related aldehyde or ketone groups. Here, we report the pharmacological activities of some thiosemicarbazones synthesized in this work. Benzophenone and derivatives were used with N(4)-phenyl-3-thiosemicarbazide to synthesize corresponding five thiosemicarbazones (1–5). Their structures were characterized by spectrometrical methods analysis IR, NMR 1H & 13C and MS. The compounds were then screened in vitro for their antiparasitic activity and toxicity on Trypanosoma brucei brucei and Artemia salina Leach respectively. The selectivity index of each compound was also determined. Four thiosemicarbazones such as 4, 2, 3 and 1 reveal interesting trypanocidal activities with their half inhibitory concentration (IC50) equal to 2.76, 2.83, 3.86 and 8.48 μM respectively, while compound 5 (IC50 = 12.16 μM) showed a moderate anti-trypanosomal activity on parasite. In toxicity test, except compound 1, which showed a half lethal concentration LC50 >281 μM, the others exerted toxic effect on larvae with LC50 of 5.56, 13.62, 14.55 and 42.50 μM respectively for thiosemicarbazones 4, 5, 3 and 2. In agreement to their selectivity index, which is greater than 1 (SI >1), these compounds clearly displayed significant selective pharmaceutical activities on the parasite tested. The thiosemicarbazones 2–5 that displayed significant anti-trypanosomal and cytoxicity activities are suggested to have anti-neoplastic and anti-cancer activities.  相似文献   

9.
A Gram-negative, polar flagella, rod-shaped bacterium LV T was isolated from a soil sample subjected to long-term manganese pollution in Hunan Province, China. Cells grow optimally on Luria–Bertani agar medium at 30 °C in the presence of 0–5.0 % (w/v) NaCl and pH 78. 16S rRNA gene sequence analysis revealed that strain LV T belonged to the genus Pseudomonas, with sequence similarity values of 98.6, 98.2, 98.7, and 97.3 % to Pseudomonas monteilii BCRC 17520 T , Pseudomonas putida BCRC 10459 T , Pseudomonas plecoglossicida BCRC 17517 T , and Pseudomonas asplenii BCRC 17131 T , respectively. The level of DNA–DNA relatedness between the five strains was <30 %. The DNA G+C content of strain LV T is 68.8 mol%. Chemotaxonomic data revealed that the strain LVT possesses ubiquinone Q-9. The polar lipid profile of strain LV T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, and phosphatidylethanolamine. The major cellular fatty acids present are C10:03-OH (12.33 %), C16:0 (23.99 %), summed feature 3(C16:1ω7c and/or C16:1ω6c), and summed feature 8(C18:1 ω7c and C18:1 ω6c). Based on the genotypic, chemotaxonomic and phenotypic data, strain LV T is distinguishable from related members of the genus Pseudomonas. Thus, strain LV T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas hunanensis sp. nov. is proposed. The type strain is LV T (=CICC 10558T = NCCB 100446T).  相似文献   

10.
This study reports the biotransformation of methylphenylacetonitriles by Brazilian marine filamentous fungus Aspergillus sydowii CBMAI 934 under eco-friendly reaction conditions. The phenylacetonitrile 1, 2-methylphenylacetonitrile 2, 3-methylphenylacetonitrile 3, and 4-methylphenylacetonitrile 4 were quantitatively biotransformed into 2-hydroxyphenylacetic 1a, 2-methylphenylacetic acid 2a, 3-methylphenylacetic acid 3a, and 4-methylphenylacetic acid 4a by enzymatic processes using whole cell as biocatalyst. The marine fungus A. sydowii CBMAI 934 is thus a promising biocatalyst for the preparation of important carboxylic acids under mild conditions (pH 7.5 and 32 °C) from nitrile compounds.  相似文献   

11.
Research on copperII 1,10-phenanththroline (phen) derivatives continues to attract interest in the context of structure and biological properties. In this paper, two metal complexes [Cu2(phen)2(μ-Cl)2]Cl2 (1), [Zn(phen)2(H2O)Cl]Cl·4H2O (2) were synthesized and characterized. The crystal structures of 1 and 2 were determined by X-ray diffraction. In order to investigate the biological properties of the prepared complexes, spectroscopic and biological studies were performed. Results of X-ray diffraction showed that 1 and 2 form two types of crystal structures in a given system: dinuclear and mono-nuclear complex. The preliminary study on the DNA cleavage activity has shown that 1 under study behaved as the chemical nucleases. The DNA binding interaction of 1 & 2 with CT-DNA has been investigated by UV–Visible and fluorescence emission spectrometry and the apparent binding constant (K app) values are 5.1 × 104 and 1.2 × 104 M?1, respectively. In addition, fluorescence spectrometry of bovine serum albumin (BSA) with 1 & 2 showed that the quenching mechanism might be a static quenching procedure with one binding sites for BSA. In addition, the cytotoxicity of 1 in vitro on tumor cells lines (MCF-7, HepG2 and HT29) was examined by MTT and showed better antitumor effect on the tested cells.  相似文献   

12.

Key Message

The critical level for SO 2 susceptibility of Populus × canescens is approximately 1.2 μL L ?1 SO 2 . Both sulfite oxidation and sulfite reduction and assimilation contribute to SO 2 detoxification.

Abstract

In the present study, uptake, susceptibility and metabolism of SO2 were analyzed in the deciduous tree species poplar (Populus × canescens). A particular focus was on the significance of sulfite oxidase (SO) for sulfite detoxification, as SO has been characterized as a safety valve for SO2 detoxification in herbaceous plants. For this purpose, poplar plants were exposed to different levels of SO2 (0.65, 0.8, 1.0, 1.2 μL L?1) and were characterized by visible injuries and at the physiological level. Gas exchange parameters (stomatal conductance for water vapor, CO2 assimilation, SO2 uptake) of the shoots were compared with metabolite levels (sulfate, thiols) and enzyme activities [SO, adenosine 5′-phosphosulfate reductase (APR)] in expanding leaves (80–90 % expanded). The critical dosage of SO2 that confers injury to the leaves was 1.2 μL L?1 SO2. The observed increase in sulfur containing compounds (sulfate and thiols) in the expanding leaves strongly correlated with total SO2 uptake of the plant shoot, whereas SO2 uptake rate was strongly correlated with stomatal conductance for water vapor. Furthermore, exposure to high concentration of SO2 revealed channeling of sulfite through assimilatory sulfate reduction that contributes in addition to SO-mediated sulfite oxidation to sulfite detoxification in expanding leaves of this woody plant species.  相似文献   

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Key message

Phytophthora infestans resistant somatic hybrids of S. × michoacanum (+) S. tuberosum and autofused 4 x S. × michoacanum were obtained. Our material is promising to introgress resistance from S. × michoacanum into cultivated potato background.

Abstract

Solanum × michoacanum (Bitter.) Rydb. (mch) is a wild diploid (2n = 2x = 24) potato species derived from spontaneous cross of S. bulbocastanum and S. pinnatisectum. This hybrid is a 1 EBN (endosperm balance number) species and can cross effectively only with other 1 EBN species. Plants of mch are resistant to Phytophthora infestans (Mont) de Bary. To introgress late blight resistance genes from mch into S. tuberosum (tbr), genepool somatic hybridization between mch and susceptible diploid potato clones (2n = 2x = 24) or potato cultivar Rywal (2n = 4x = 48) was performed. In total 18,775 calli were obtained from postfusion products from which 1,482 formed shoots. The Simple Sequence Repeat (SSR), Cleaved Amplified Polymorphic Sequences (CAPS) and Random Amplified Polymorphic DNA (RAPD) analyses confirmed hybrid nature of 228 plants and 116 autofused 4x mch. After evaluation of morphological features, flowering, pollen stainability, tuberization and ploidy level, 118 somatic hybrids and 116 autofused 4x mch were tested for late blight resistance using the detached leaf assay. After two seasons of testing three somatic hybrids and 109 4x mch were resistant. Resistant forms have adequate pollen stainability for use in crossing programme and are a promising material useful for introgression resistance from mch into the cultivated potato background.  相似文献   

15.
The preliminary cytotoxic effect of 4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide hydrochloride (1)—a potent topoisomerase II inhibitor—was measured using a MTT assay. It was found that the compound decreased the number of viable cells in both estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231breast cancer cells, with IC50 values of 146?±?2 and 132?±?2 μM, respectively. To clarify the molecular basis of the inhibitory action of 1, molecular docking studies were carried out. The results suggest that 1 targets the ATP binding pocket.
Figure
4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide hydrochloride  相似文献   

16.
A dimeric GdAAZTA-like complex (AAZTA is 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) bearing an adamantyl group (Gd2 L1) able to form strong supramolecular adducts with specific hosts such as β-cyclodextrin (β-CD), poly-β-CD, and human serum albumin (HSA) is reported. The relaxometric properties of Gd2 L1 were investigated in aqueous solution by measuring the 1H relaxivity as a function of pH, temperature, and magnetic field strength. The relaxivity of Gd2 L1 (per Gd atom) at 40 MHz and 298 K is 17.6 mM?1 s?1, a value that remains almost constant at higher fields owing to the great compactness and rigidity of the bimetallic chelate, resulting in an ideal value for the rotational correlation time for high-field MRI applications (1.5–3.0 T). The noncovalent interaction of Gd2 L1 with β-CD, poly-β-CD, and HSA and the relaxometric properties of the resulting host–guest adducts were investigated using 1H relaxometric methods. Relaxivity enhancements of 29 and 108 % were found for Gd2 L1–β-CD and Gd2 L1–poly-β-CD, respectively. Binding of Gd2 L1 to HSA (K A = 1.2 × 104 M?1) results in a remarkable relaxivity of 41.4 mM?1 s?1 for the bound form (+248 %). The relaxivity is only limited by the local rotation of the complex within the binding site, which decreases on passing from Gd2 L1–β-CD to Gd2 L1–HSA. Finally, the applicability of Gd2 L1 as tumor-targeting agent through passive accumulation of the HSA-bound adduct was evaluated via acquisition of magnetic resonance images at 1 T of B16-tumor-bearing mice. These experiments indicate a considerable signal enhancement (+160 %) in tumor after 60 min from the injection and a very low hepatic accumulation.  相似文献   

17.
The interaction of a water-soluble dinuclear nickel(II) complex, [Ni2(EGTB)(CH3CN)4](ClO4)4·4H2O (EGTB = ethylene glycol-bis(β-aminoethyl ether) N,N,N′,N′-tetrakis(2-benzimidazoyl)) (1), and bovine serum albumin (BSA) was investigated under physiological conditions using fluorescence, synchronous fluorescence, UV–vis absorption and circular dichroism (CD). The experimental results suggested that the nickel(II) complex could bind to BSA with binding constant (K) ~ 104 M?1 and quench the intrinsic fluorescence of BSA through a static quenching mechanism. The thermodynamic parameters, ΔG°, ΔH°, and ΔS°, calculated at different temperatures, indicated that the binding reaction was spontaneous and electrostatic interactions played a major role in this association. Based on the number of binding sites, it was considered that one molecule of complex 1 could bind to a single site or two sites of the BSA molecule or the two binding modes coexisted. In view of the results of site marker competition experiments, the reactive sites of BSA to complex 1 mainly located in subdomain IIA (site I) and subdomain IIIA (site II) of BSA. Moreover, the binding distance, r, between donor (BSA) and acceptor (complex 1) was 5.13 nm according to Förster nonradiation energy transfer theory. Finally, as shown by the UV–vis absorption, synchronous fluorescence and CD, complex 1 could induce conformation and microenvironmental changes of BSA. The results obtained herein will be of biological significance in toxicology investigation and anticancer metallodrug design.  相似文献   

18.
A series of new silver(I) saccharinate (sac) complexes, [Ag2(sac)2(μ-dppm)H2O]·H2O (1), {[Ag2(μ-sac)2(μ-dppe)]·3H2O·CH2Cl2} n (2), [Ag2(μ-sac)2(μ-dppp)] n (3), and [Ag(sac)(μ-dppb)] n (4) [dppm is 1,1-bis(diphenylphosphino)methane, dppe is 1,2-bis(diphenylphosphino)ethane, dppp is 1,3-bis(diphenylphosphino)propane, and dppb is 1,4-bis(diphenylphosphino)butane], have been synthesized and characterized by C, H, N elemental analysis, IR spectroscopy, 1H NMR, 13C NMR, and 31P NMR spectroscopy, electrospray ionization mass spectrometry, and thermogravimetry–differential thermal analysis. Single-crystal X-ray studies show that the diphosphanes act as bridging ligands to yield a dinuclear complex (1) and one-dimensional coordination polymers (2 and 4), whereas the sac ligand adopts a μ2-N/O bridging mode in 2, and is N-coordinated in 1 and 4. The interaction of the silver(I) complexes with fish sperm DNA was investigated using UV–vis spectroscopy, fluorescence spectroscopy, and agarose gel electrophoresis. The binding studies indicate that the silver(I) complexes can interact with fish sperm DNA through intercalation, and complexes 1 and 3 have the highest binding affinity. The gel electrophoresis assay further confirms the binding of the complexes with the pBR322 plasmid DNA. The minimum inhibitory concentrations of the complexes indicate that complex 1 exhibits very high antibacterial activity against standard bacterial strains of Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus, being much higher than those of AgNO3, silver sulfadiazine, ciprofloxacin, and gentamicin. Moreover, complexes 13 exhibit very high cytotoxic activity against A549 and MCF-7 cancer cell lines, compared with AgNO3 and cisplatin. The bacterial and cell growth inhibitions of the silver(I) complexes are closely related to their DNA binding affinities.  相似文献   

19.
Cu(I)-mediated [3+2]cycloaddition between azides and alkynes has evolved into a valuable bioconjugation tool in radiopharmaceutical chemistry. We have developed a simple, convenient and reliable radiosynthesis of 4-[18F]fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([ 18 F]F-SA) as a novel aromatic sulfonamide-based click chemistry building block. [ 18 F]F-SA could be prepared in a remotely controlled synthesis unit in 32 ± 5 % decay-corrected radiochemical yield in a total synthesis time of 80 min. The determined lipophilicity of [ 18 F]F-SA (logP = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [ 18 F]F-SA as click chemistry building block was demonstrated by the labeling of a model peptide (phosphopeptide), protein (HSA), and oligonucleotide (L-RNA). The obtained radiochemical yields were 77 % (phosphopeptide), 55–60 % (HSA), and 25 % (L-RNA), respectively. Despite the recent emergence of a multitude of highly innovative novel bioconjugation methods for 18F labeling of biopolymers, Cu(I)-mediated click chemistry with [ 18 F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter 18F.  相似文献   

20.

Key message

This study demonstrates for the first time that resistance to different root lesion nematodes ( P. neglectus and P. penetrans ) is controlled by a common QTL. A major resistance QTL ( Rlnnp6H ) has been mapped to chromosome 6H using two independent barley populations.

Abstract

Root lesion nematodes (Pratylenchus spp.) are important pests in cereal production worldwide. We selected two doubled haploid populations of barley (Igri × Franka and Uschi × HHOR 3073) and infected them with Pratylenchus penetrans and Pratylenchus neglectus. Nematode multiplication rates were measured 7 or 10 weeks after infection. In both populations, continuous phenotypic variations for nematode multiplication rates were detected indicating a quantitative inheritance of resistance. In the Igri × Franka population, four P. penetrans resistance QTLs were mapped with 857 molecular markers on four linkage groups (2H, 5H, 6H and 7H). In the Uschi × HHOR 3073 population, eleven resistance QTLs (P. penetrans and P. neglectus) were mapped with 646 molecular markers on linkage groups 1H, 3H, 4H, 5H, 6H and 7H. A major resistance QTL named Rlnnp6H (LOD score 6.42–11.19) with a large phenotypic effect (27.5–36.6 %) for both pests was mapped in both populations to chromosome 6H. Another resistance QTL for both pests was mapped on linkage group 5H (Igri × Franka population). These data provide first evidence for common resistance mechanisms against different root lesion nematode species. The molecular markers are a powerful tool for the selection of resistant barley lines among segregating populations because resistance tests are time consuming and laborious.  相似文献   

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