Search results for "Biochemistry"
showing 10 items of 20172 documents
Synthesis, biological evaluation, and structure-activity relationship study of novel cytotoxic aza-caffeic acid derivatives.
2010
Abstract Three series of aza-caffeic acid derivatives with different linkers were designed and synthesized. Each of the synthesized derivatives was then used in cytotoxicity screening on either 8 or 12 human cancer cell lines. The structure–activity relationships on three structural regions A, B, and C are analyzed in detail, indicating that a nine bond linker B, containing a piperazine unit, is the most favorable linker leading to the generation of molecules with potent cytotoxicities. Compound ( E )-1-(4-(3,4-dichlorobenzyl)piperazin-1-yl)-3-(4-(4-ethoxybenzyloxy)-3,5-dimethoxyphenyl)prop-2-en-1-one ( 80 ) exhibited the most significant and selective cytotoxicity to KB, BEL7404, K562, and…
Synthesis of azoxystrobin transformation products and selection of monoclonal antibodies for immunoassay development
2012
The use of agrochemicals for crop protection may result in the presence of toxic residues in soils and aquatic environments, besides in foodstuffs. Most often just the parent compound is included in the definition of pesticide residue, even though chemicals resulting from biotransformation and degradation routes might also be of toxicological relevance. Azoxystrobin is a broad-spectrum systemic fungicide widely used worldwide to combat pathogenic fungi affecting plants. We herein report the synthesis and detailed chemical characterization of several of the most relevant metabolites and degradates of azoxystrobin. These compounds were further employed as ligands for screening a collection of…
Synthesis of fluorine-18 labeled sulfonureas as ?-cell imaging agents
2001
Tolbutamide (1) and glyburide (7) are hypoglycemic drugs used to stimulate insulin secretion in type 2 diabetic patients. We have synthesized their fluorine-18 labeled analogs, 1-[(4-[ 18 F]fluorobenzenesulfonyl)]-3-butyl]urea (p-[ 18 F]fluorotolbutamide, 3a) and N-{4-[β-(2-[ 18 F]fluoroethoxybenzene carboxamido)ethyl]benzenesulfonyl)-N'-cyclohexylurea (2-[ 18 F]fluoroethoxyglyburide, 6a) as β-cell imaging agents. Compound 3a was synthesized via two approaches: One-step synthesis via nucleophilic substitution of p-nitrotolbutamide (2) with K[ 18 F]/Kryptofix 2.2.2 in either CH 3 CN or DMSO gave a complicated mixture; a two-step synthesis via preparation and reaction of 4-[ 18 F]fluorobenzen…
7-O-acetyl-GD3 in human T-lymphocytes is detected by a specific T-cell-activating monoclonal antibody.
1995
The monoclonal antibody U5, which is a potent inducer of proliferation in human T-cells, was found to bind to an alkali-sensitive derivative of ganglioside GD3. Using immunochemical and spectroscopic methods, the structure of the U5 antigen was determined as 7-O-acetyl-GD3. The antibody U5 did not react with 9-O-acetyl-GD3 and bound severalfold more stronger to 7-O-acetyl-GD3 than to GD3. U5 is the first antibody known to detect preferentially 7-O-acetyl-GD3. Flow cytometric analysis showed that each major class of human leukocytes contained a significant fraction of cells binding the U5 antibody.
Production and characterization of a monoclonal antibody to the trichothecene mycotoxin diacetoxyscirpenol.
1988
A monoclonal antibody was obtained by the fusion of mouse myeloma cells with splenocytes isolated from Balb/c mice, which had been immunized with diacetoxyscirpenol-hemiglutarate (DAS-hemiglutarate) and verrucarol-hemiglutarates covalently bound to ethylenediamine-modified bovine serum albumin. The anti-DAS-antibody that could be induced was of the IgM type with kappa-chains. The titer of the monoclonal anti-DAS-antibody in ascites fluid obtained from mice injected the selected cell line was much higher than those of conventional antisera. An enzyme-linked immunosorbent assay based on the competitive binding principle in which the antibody was applied had a sensitivity of 1 ng DAS per assay…
Development and biological investigations of hypoxia-sensitive prodrugs of the tyrosine kinase inhibitor crizotinib
2019
Despite the huge success of tyrosine kinase inhibitors as anticancer agents, severe side effects are a major problem. In order to overcome this drawback, the first hypoxia-activatable 2-nitroimidazole-based prodrugs of the clinically approved ALK and c-MET inhibitor crizotinib were developed. The 2-aminopyridine functionality of crizotinib (essential for target kinase binding) was considered as ideal position for prodrug derivatization. Consequently, two different prodrugs were synthesized with the nitroimidazole unit attached to crizotinib either via carbamoylation (A) or alkylation (B) of the 2-aminopyridine moiety. The successful prodrug design could be proven by docking studies and a dr…
Humoral immunotherapy of multiple myeloma: perspectives and perplexities
2010
IMPORTANCE OF THE FIELDS Multiple myeloma (MM) is a hematological malignancy still remaining incurable despite the various therapies available, mainly because of the high fraction of refractory/relapsing cases. Therefore, the development of novel therapeutic approaches is urgently needed to overcome conventional treatment resistance. AREAS COVERED IN THIS REVIEW: In the era of targeted therapies, treatments combining a high specificity for neoplastic cells and the capability to interfere with environmental signals should be regarded as the weapons of choice. Monoclonal antibody (mAb)-based humoral immunotherapy could satisfy both these requirements when applied to MM. Indeed, many of the mo…
Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapy
2003
Renal cell carcinoma (RCC) represents the most common malignant tumor in the kidney and is resistant to conventional therapies. The diagnosis of RCC is often delayed leading to progression and metastatic spread of the disease. Thus, validated markers for the early detection of the disease as well as selection of patients undergoing specific therapy is urgently needed. Using treatment with the monoclonal antibody (mAb) G250 as a model, proteome-based strategies were implemented for the identification of markers which may allow the discrimination between responders and nonresponders prior to application of G250-mediated immunotherapy. Flow cytometry revealed G250 surface expression in approxi…
BCR-ABL as a target for novel therapeutic interventions.
2002
The BCR-ABL oncogene is the result of a reciprocal translocation between the long arms of chromosome 9 and 22 t(9; 22). There is good experimental evidence demonstrating that BCR-ABL is the single causative abnormality in chronic myeloid leukaemia (CML), making it a unique model for the development of molecular targets. In addition to CML, BCR-ABL transcripts can be found in a minority of acute lymphoblastic leukaemias and very rarely in acute myeloid leukaemia (AML). Elucidating the molecular mechanisms and downstream pathways of BCR-ABL has led to the design of several novel therapeutic approaches. In this review, molecular targeting of BCR-ABL will be discussed based on the inhibition of…
In utero exposure to mixtures of xenoestrogens and child neuropsychological development.
2014
BACKGROUND: To date, no epidemiological studies have explored the impact and persistence of in utero exposure to mixtures of xenoestrogens on the developing brain. We aimed to assess whether the cumulative effect of xenoestrogens in the placenta is associated with altered infant neuropsychological functioning at two and at four years of age, and if associations differ among boys and girls. METHODS: Cumulative prenatal exposure to xenoestrogens was quantified in the placenta using the biomarker Total Effective Xenoestrogen Burden (TEXB-alpha) in 489 participants from the INMA (Childhood and the Environment) Project. TEXB-alpha was split in tertiles to test its association with the mental and…