Search results for "Growth inhibition"
showing 10 items of 63 documents
Combined Targeting of the Menin-MLL1 Chromatin Complex and FLT3 As a Novel Therapeutic Concept Against NPM1 Mutant or MLL-Rearranged AML with Mutated…
2019
NPM1mutant (NPM1mut) and MLL1-rearranged (MLL-r) acute myeloid leukemias (AMLs) exhibit aberrant expression of HOX and MEIS1 transcription factors and commonly harbor an activating mutation in the receptor tyrosine kinase FLT3. Pharmacologic inhibition of the menin-MLL1 complex reverses leukemogenic gene expression including MEIS1 and FLT3 and represents a therapeutic opportunity for the treatment of these leukemias. Here, we investigate the contribution of the menin-MLL1 complex to leukemic FLT3 signaling and assess the therapeutic potential of dual menin-MLL1 and FLT3 targeting. First, we performed RNA sequencing to delineate transcriptional changes associated with menin-MLL1 inhibition (…
ChemInform Abstract: Synthesis and Antineoplastic Activity of New 4-Diazopyrazole Derivatives.
2010
Several new 4-diazopyrazole derivatives were synthesized by reaction of 1-(R-substituted)phenyl-3-methyl-5-benzamidopyrazoles with a sevenfold excess of nitrous acid in acetic media. The compounds were tested at 20 microM concentration for their antineoplastic activity in vitro against Raji (human Burkitt lymphoma), K562 (human chronic myelogenous leukemia) and U937 (human histiocytic lymphoma) cell lines. They showed a percent of growth inhibition in the range 23.4-100%.
Phytosterols: to be or not to be toxic; that is the question
2008
Plant sterols (phytosterols) are membrane constituents of all plants with a structure analogous to that of cholesterol. Thus, phytosterols have either an additional methyl or ethyl group on the carbon-24 position or an additional double bond in the side chain (1) . Noteworthy, in patients with the rare inherited disease of phytosterolaemia characterized by a hyperabsorption and diminished biliary secretion of cholesterol and phytosterols as well as by tendon and tuberous xanthoma, elevated plasma concentrations of phytosterols (campesterol, sitosterol) have been shown to constitute a risk factor for premature atherosclerosis (2) . However, whether plasma concentrations of campesterol and si…
Antitumor effects of dehydroxymethylepoxyquinomicin, a novel nuclear factor-kappaB inhibitor, in human liver cancer cells are mediated through a reac…
2009
Activation of the nuclear transcription factor-kappa B (NF-kappa B) has been implicated in liver tumorigenesis. We evaluated the effects of a novel NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in two human liver cancer cell lines HA22T/VGH and HuH-6. DHMEQ treatment dose dependently decreased the DNA-binding capacity of the NF-kappa B p65 subunit, inhibited cell growth and proliferation, and increased apoptosis as shown by caspase activation, release of cytochrome c, poly(ADP-ribose) polymerase cleavage, and down-regulation of survivin. DHMEQ also induced a dose-dependent activation of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling, …
Development of Novel Selective Peptidomimetics Containing a Boronic Acid Moiety, Targeting the 20S Proteasome as Anticancer Agents
2014
This paper describes the design, synthesis, and biological evaluation of peptidomimetic boronates as inhibitors of the 20S proteasome, a validated target in the treatment of multiple myeloma. The synthesized compounds showed a good inhibitory profile against the ChT-L activity of 20S proteasome. Compounds bearing a β-alanine residue at the P2 position were the most active, that is, 3-ethylphenylamino and 4-methoxyphenylamino (R)-1-{3-[4-(substituted)-2-oxopyridin-1(2H)-yl]propanamido}-3-methylbutylboronic acids (3 c and 3 d, respectively), and these derivatives showed inhibition constants (Ki ) of 17 and 20 nM, respectively. In addition, they co-inhibited post glutamyl peptide hydrolase act…
An alternative set of test to bioassay for bioinsecticides
2010
The development of an assay to determine insecticidal properties for either biological and conventional plant protection products plays an important role on the early screening of potential pathogens or derived toxins candidates. The standard methods for the evaluation it has been by bioassay, especially determination of LD50 or LC 50 requiring the use of relatively large numbers of insects and toxin tests. There are several problems connected with these bioassays: availability of insects and in the right life stage, mass producing the candidate species, preparation, reproducibly and costs relative to intensive manpower. These aspects are really important especially when bio-insectides shou…
Synthesis and in vitro antileukemic activity of new 4-triazenopyrazole derivatives
2003
Several new 4-(3,3-dimethyltriazeno)-5-benzamidopyrazole derivatives were prepared by reacting 4-diazo-5-benzamidopyrazole derivatives with dimethylamine. The compounds were tested at 10 microM for their vitro antileukemic activity against K562 (Human chronic myelogenous leukemia) and Raji (human Burkitt limphoma ) cell lines. Dacarbazine and methotrexate were used for comparative purpose. The 3-methyl-4-(3,3-dimethyltriazeno)-5-(substituted benzamido)pyrazoles, bearing the pyrazole nucleus free at 1 position, resulted more active than the 1-(substituted phenyl)-3-methyl-4-(3,3-dimethyltriazeno)-5-benzamidopyrazoles. Dacarbazine at 10 microM showed no activity in the above tests. The observ…
Cytotoxicity and inhibition of P-glycoprotein by selected medicinal plants from Thailand.
2014
Abstract Ethnopharmacological relevance Thai medicine has a long tradition of tonifying medicinal plants. In the present investigation, we studied the flower extracts of Jasminum sambac, Mammea siamensis, Mesua ferrea, Michelia alba, Mimusops elengi, and Nelumbo nucifera and speculated that these plants might influence metabolism and substance flow in the body. Materials and methods Isolation of porcine brain capillary endothelial cells (PBCECs) as well as multidrug-resistance CEM/ADR5000 leukemia cells, MDA-M;B-231 breast cancer, U-251 brain tumor, and HCT-116 colon cancer cells were used. The calcein-acetoxymethylester (AM) assay was used to measure inhibition of P-glycoprotein transport.…
In Vitro and In Vivo Antimalarial Activity Assays of Seeds from Balanites aegyptiaca: Compounds of the Extract Show Growth Inhibition and Activity ag…
2011
Balanites aegyptiaca(Balanitaceae) is a widely grown desert plant with multiuse potential. In the present paper, a crude extract fromB. aegyptiacaseeds equivalent to a ratio of 1 : 2000 seeds to the extract was screened for antiplasmodial activity. The determined IC50value for the chloroquine-susceptiblePlasmodium falciparumNF54 strain was 68.26 . Analysis of the extract by gas chromatography-mass spectrometry detected 6-phenyl-2(H)-1,2,4-triazin-5-one oxime, an inhibitor of the parasitic M18 Aspartyl Aminopeptidase as one of the compounds which is responsible for thein vitroantiplasmodial activity. The crude plant extract had a of 2.35 and showed a dose-dependent response. After depletion…
The Arabidopsis Copper Transporter COPT1 Functions in Root Elongation and Pollen Development
2004
Copper plays a dual role in aerobic organisms, as both an essential and a potentially toxic element. To ensure copper availability while avoiding its toxic effects, organisms have developed complex homeostatic networks to control copper uptake, distribution, and utilization. In eukaryotes, including yeasts and mammals, high affinity copper uptake is mediated by the Ctr family of copper transporters. This work is the first report on the physiological function of copper transport in Arabidopsis thaliana. We have studied the expression pattern of COPT1 in transgenic plants expressing a reporter gene under the control of the COPT1 promoter. The reporter gene is highly expressed in embryos, tric…