Home About us Contact
|
Home About us Contact | ||
|
|
||
High Inhibition (high + inhibition)
Selected AbstractsPolycarbonate microspheres containing tumor necrosis factor-, genes and magnetic powder as potential cancer therapeuticsJOURNAL OF APPLIED POLYMER SCIENCE, Issue 5 2008Bin Hu Abstract Amphiphilic polycarbonate copolymers including methoxy-terminated poly(ethylene glycol)- co -poly (5,5-dimethyl trimethylene carbonate) [Poly(PEG- b -TMC)] and poly(ethylene glycol)- co -poly(trimethylene carbonate) [Poly(PEG- b -DTC)] were synthesized. The water-in-oil-in-water (W/O/W) solvent evaporation technique was adopted to produce anticancer magnetic Poly(PEG- b -DTC) microspheres containing tumor necrosis factor-, (TNF-,) genes and Fe3O4 magnetic ultrafine powder. Drug release studies showed that the microspheres can sustain a steady release rate of TNF-, genes in 0.1M phosphate buffer saline solution in vitro for up to 60 h. In vitro cytotoxicity assays demonstrated that the microspheres have high inhibition and antitumor action to human hepatocellular carcinoma (Bel-7204) cells in vitro. In vivo inhibition on the growth of hepatic carcinomas and histopathologic observation indicated that the microspheres possess a markedly high antitumor activity to human hepatocellular carcinoma (Bel-7204). © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Selectivity of N -aroyl- N,-arylthioureas towards 2-(1,3-dioxo-1H -inden-2(3H)-ylidene)malononitrile.JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 20102- d][, 3]- thiazepin-2(6H)-ylidene)-4-arylamides of antitumor, New synthesis of (Z)- N -((E)-4-amino-1-aryl-5-cyano-6-oxo-1H -indeno[, antioxidant activities The reaction between N -aroyl- N,-arylthioureas with 2-(1,3-dioxoindan-2-ylidene)malononitrile furnished indeno[1,2- d][1,3]thiazepines in 70,85% yields. The mechanism of the products' formation is discussed. Some of the products showed effective antitumor and antioxidant activities. The results revealed that compound indenothiazepine derivative showed a high inhibition of the cell growth of Hep-G2 cells is compared with the growth of untreated control cells, as concluded from their low IC50 value 21.73 ,M. On the other hand, two indenothiazepine derivatives have an effective antioxidant activity with SC50 values of 62.5 mM and 87.4 mM, respectively. J. Heterocyclic Chem., (2010). [source] Purification of citrus limonoids and their differential inhibitory effects on human cytochrome P450 enzymesJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2007Shibu M Poulose Abstract Recent studies demonstrated that citrus limonoids and flavonoids possess numerous health promoting properties. In the present study, glucosides of limonoids and flavonoids were purified from citrus molasses and limonoid aglycones from citrus seeds. Glucosides were separated on styrene (divinylbenzene), Q-sepharose resins with increasing concentration of sodium chloride. A pH-dependent cold precipitation was carried out for the isolation of naringin in large quantity. Major aglycones such as limonin and nomilin were isolated from seeds by direct crystallization and minor limonoids were purified by vacuum liquid chromatography. The structures of the isolated compounds were confirmed by NMR spectra. Individual limonoids were tested for O -dealkylase and hydroxylase activities of human cytochrome P450 (CYP) isoenzymes such as CYP1A2, CYP1B1, CYP3A4 and CYP19, using ethoxyresorufin, methoxyresorufin and dibenzylfluorescein as substrates. Partial to high inhibition of CYPs was observed in dose-dependent assays. Significant (P < 0.001) reductions in enzyme activities were observed with purified compounds above 2 µmol. Kinetic analyses indicated that limonin glucoside inhibited CYP19 competitively (IC50, 7.1 µ mol L,1), whereas Nomilinic acid glucoside inhibited it noncompetitively (IC50, 9.4 µ mol,1). Nomilinic acid glucoside was the most potent limonoid, with an overall IC50 of < 10 µ mol, for all the enzymes tested. The differential inhibition of CYPs can be ascribed to structural variations of the limonoid nucleus. Limonoid inhibition of key CYPs involved in carcinogenesis supports growing evidence that citrus limonoids act as anticancer agents. Copyright © 2007 Society of Chemical Industry [source] Antimalarial compounds from Kniphofia foliosa rootsPHYTOTHERAPY RESEARCH, Issue 6 2005Abraham Abebe Wube Abstract During the course of screening Ethiopian medicinal plants for their antimalarial properties, it was found that the dichloromethane extract of the roots of Kniphofia foliosa Hochst. (Asphodelaceae), which have long been used in the traditional medicine of Ethiopia for the treatment of abdominal cramps and wound healing, displayed strong in vitro antiplasmodial activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum with an ED50 value of 3.8 µg/mL and weak cytotoxic activity against KB cells with an ED50 value of 35.2 µg/mL. Five compounds were isolated from the roots and evaluated for their invitro antimalarial activity. Among the compounds tested, 10-(chrysophanol-7,-yl)-10-(,)-hydroxychrysopanol-9-anthrone and chryslandicin, showed a high inhibition of the growth of the malaria parasite, P. falciparum with ED50 values of 0.260 and 0.537 µg/mL, respectively, while the naphthalene derivative, 2-acetyl-1-hydroxy-8-methoxy-3-methylnaphthalene, exhibited a less significant antimalarial activity with an ED50 value of 15.4 µg/mL. To compare the effect on the parasite with toxicity to mammalian cells, the cytotoxic activities of the isolated compounds against the KB cell line were evaluated and 10-(chrysophanol-7,-yl)-10-(,)-hydroxychrysopanol-9-anthrone and chryslandicin displayed very low toxicity with ED50 values of 104 and 90 µg/mL, respectively. This is the first report of the inhibition of the growth of P. falciparum by anthraquinone-anthrone dimers and establishes them as a new class of potential antimalarial compounds with very little host cell toxicity. Copyright © 2005 John Wiley & Sons, Ltd. [source] Thieno[2,3- d]pyrimidines in the Synthesis of Antitumor and Antioxidant AgentsARCHIV DER PHARMAZIE, Issue 5 2010Ashraf A. Aly Abstract Dimethyl acetylenedicarboxylate, ethyl propiolate, and E -dibenzoylethylene react with thienopyrimidines (cyclo-pentyl, -hexyl, and -heptyl) derivatives to form thiazolo[3,2- a]thieno-[2,3- d]pyrimidin-2-ylidene) acetates, thieno[2,3- d]pyrimidin-2-ylthioacrylates, and thieno[2,,3,:4,5]pyrimido[2,1- b][1,3]thiazin-6-ones, respectively. Reactions proceed via cyclization and thio-addition processes. Some derivatives of thienopyrimidines showed high inhibition of Hep-G2 cell growth compared with the growth of untreated control cells. However, the fused heptyl of thienopyrimidothiazines indicates a promising specific antitumor agent against Hep-G2 cells with IC50 < 20 ,M. [source] Biosynthesis of New Indigoid Inhibitors of Protein Kinases Using Recombinant Cytochrome P450 2A6CHEMISTRY & BIODIVERSITY, Issue 1 2005Zhongliu-Liu Wu Glycogen synthase kinase-3 (GSK-3) is a potential drug target for a number of human diseases. Some indigoids have been found to be potent inhibitors of GSK-3, and individual compounds with better activity, specificity, and solubility are desired. In this work, a new disubstituted indigoid generation system was developed with a tryptophanase-deficient Escherichia coli strain as a host to express the human cytochrome P450 2A6 mutant L240C/N297Q, which catalyzes the oxidation of indole to isatin and indoxyl, which in turn react to generate indigoids. Forty-five substituted 1H -indoles from commercial sources were used as substrates in the system, and indigoid mixtures were tested as potential inhibitors of GSK-3. After preliminary screening, cell extracts with high inhibitory activity towards GSK-3,/, were fractionated, and the IC50 values of twelve individual indigoids were measured for GSK-3,/, as well as the protein kinases CDK1/cyclinB and CDK5/p25. Several indigoids, including an indigo, showed stronger inhibition than found in previous work. The most potent towards GSK-3,/,, dimethyl indirubin 5,5,-dicarboxylate (IC50 of 51,nM), was modified by chemical reactions. One product, indirubin 5,5,-dicarboxylic acid 5-methyl ester, inhibited GSK-3,/, with an IC50 of 14,nM and selectivity nearly 40-fold over CDK1 and CDK5. Indirubin-5-5,-dicarbonitrile was also modified to the corresponding 3,-oxime, which had low specificity but showed very high inhibition of all three kinases with IC50 values of 5, 13, and 10,nM towards GSK-3,/,, CDK1, and CDK5, respectively. Thus, this system has the potential to generate new indigoids with therapeutic potential. [source] | ||||||||||