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Cytotoxic Properties (cytotoxic + property)
Selected AbstractsSynthesis of 2,6-Diphenylpyrazine Derivatives and Their DNA Binding and Cytotoxic Properties.CHEMINFORM, Issue 17 2006Nathalie Dias Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Synthesis and antiproliferative evaluation of new aryl substituted pyrido[3,,2,:5,6]thiopyrano[4,3- c]pyrazolesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 7 2005G. Primofiore The preparation and the cytotoxic properties of new derivatives of the planar pyrido[3,,2,:5,6]thiopyrano-[4,3- c]pyrazole system, carrying an arylic side group in the 1 or 2 positions, are described. The novel substituted derivatives were obtained by reaction of suitable arylhydrazines with the appropriate key intermediate 3-hydroxymethylene-2,3-dihydrothiopyrano[2,3- b]pyridin-4(4H)-ones. Moreover the preparation was reported of the 2-carboxamidophenyl derivatives, which was accomplished from the previously obtained pyrido[3,,2,:5,6]thiopyrano[4,3- c]pyrazole nucleus, by reaction with phenylisocyanate. All the new compounds were evaluated for their antiproliferative ability, by an in vitro assay on human tumor cell lines (HL-60 and HeLa). [source] Structural studies and model membrane interactions of two peptides derived from bovine lactoferricinJOURNAL OF PEPTIDE SCIENCE, Issue 7 2005Leonard T. Nguyen Abstract The powerful antimicrobial properties of bovine lactoferricin (LfcinB) make it attractive for the development of new antimicrobial agents. An 11-residue linear peptide portion of LfcinB has been reported to have similar antimicrobial activity to lactoferricin itself, but with lower hemolytic activity. The membrane-binding and membrane-perturbing properties of this peptide were studied together with an amidated synthetic version with an added disulfide bond, which was designed to confer increased stability and possibly activity. The antimicrobial and cytotoxic properties of the peptides were measured against Staphylococcus aureus and Escherichia coli and by hemolysis assays. The peptides were also tested in an anti-cancer assay against neuroblastoma cell lines. Vesicle disruption caused by these LfcinB derivatives was studied using the fluorescent reporter molecule calcein. The extent of burial of the two Trp residues in membrane mimetic environments were quantitated by fluorescence. Finally, the solution NMR structures of the peptides bound to SDS micelles were determined to provide insight into their membrane bound state. The cyclic peptide was found to have greater antimicrobial potency than its linear counterpart. Consistent with this property, the two Trp residues of the modified peptide were suggested to be embedded deeper into the membrane. Although both peptides adopt an amphipathic structure without any regular ,-helical or ß-sheet conformation, the 3D-structures revealed a clearer partitioning of the cationic and hydrophobic faces for the cyclic peptide. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Ex situ cultivation of Aplysinaaerophoba close to in situ conditions: ecological, biochemical and histological aspectsMARINE ECOLOGY, Issue 2 2008Anne Klöppel Abstract Sponges provide the largest number of biologically active natural products known from the marine environment and continue to be a very well studied phylum of marine fauna. The Mediterranean sponge Aplysina aerophoba accumulates brominated isoxazoline alkaloids such as Aplysinamisin-1, Aerophobin-2, Isofistularin-3 and the biotransformation product Aeroplysinin-1, which possesses, for example, antibiotic and cytotoxic properties. Until now, it is still being discussed which organisms , the sponge itself or associated microorganisms , are responsible for metabolite production. For cultivating Aplysina individuals under ex situ conditions, we surveyed relevant ecological factors in situ and controlled them in our aquarium system. We maintained A. aerophoba for more than 9 months and analysed changes of metabolite content and composition, microbial association as well as morphology in situ and ex situ under different light exposure. Although sponges showed slight reduction during maintenance, ex situ cultivation similar to in situ conditions provides a promising method to keep sponges and obtain their bioactive metabolites. [source] Antitumor activity of total alkaloid fraction of solanum pseudocapsicum leavesPHYTOTHERAPY RESEARCH, Issue 9 2003Shrishailappa Badami Abstract The total alkaloid fraction of the methanolic extract of Solanum pseudocapsicum leaves was tested for its in-vivo antitumor activity against Dalton's Lymphoma Ascites model in mice. The total alkaloid fraction at 2.5 and 5.0 mg/kg body weight doses exhibited antitumor activity as revealed by the signi,cant increase in the mean survival time and the percentage increase in life span of tumor bearing mice. The antitumor activity observed may be due to its cytotoxic properties. However the treatment caused a signi,cant decrease in the body weight below the normal indicating the toxicity of the treatment. Copyright © 2003 John Wiley & Sons, Ltd. [source] Structural elucidation of metabolites of ginkgolic acid in rat liver microsomes by ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry and hydrogen/deuterium exchangeRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 13 2009Z. H. Liu Ginkgolic acids have been shown to possess allergenic as well as genotoxic and cytotoxic properties. The question arises whether the metabolism of ginkgolic acids in the liver could decrease or increase their toxicity. In this study, the invitro metabolism of ginkgolic acid (15:1, GA), one component of ginkgo acids, was investigated as a model compound in Sprague-Dawley rat liver microsomes. The metabolites were analyzed by ultra-performance liquid chromatography coupled with photodiode array detector/negative-ion electrospray ionization tandem mass spectrometry (UPLC-PDA/ESI-MS/MS) and hydrogen/deuterium (H/D) exchange. The result showed that the benzene ring remained unchanged and the oxidations occurred at the side alkyl chain in rat liver microsomes. At least eight metabolites were found. Among them, six phase I metabolites were tentatively identified. This study might be useful for the investigation of toxicological mechanism of ginkgolic acids. Copyright © 2009 John Wiley & Sons, Ltd. [source] Action Mechanisms of the Secondary Metabolite Euplotin C: Signaling and Functional Role in EuplotesTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 5 2008FRANCESCA TRIELLI ABSTRACT. Among secondary metabolites, the acetylated hemiacetal sesquiterpene euplotin C has been isolated from the marine, ciliated protist Euplotes crassus, and provides an effective mechanism for reducing populations of potential competitors through its cytotoxic properties. However, intracellular signaling mechanisms and their functional correlates mediating the ecological role of euplotin C are largely unknown. We report here that, in E. vannus (an Euplotes morphospecies that does not produce euplotin C and shares with E. crasssus the same interstitial habitat), euplotin C rapidly increases the intracellular concentration of both Ca2+ and Na+, suggesting a generalized effect of this metabolite on cation transport systems. In addition, euplotin C does not induce oxidative stress, but modulates the electrical properties of E. vannus through an increase of the amplitude of graded action potentials. These events parallel the disassembling of the ciliary structures, the inhibition of cell motility, the occurrence of aberrant cytoplasmic vacuoles, and the rapid inhibition of phagocytic activity. Euplotin C also increases lysosomal pH and decreases lysosomal membrane stability of E. vannus. These results suggest that euplotin C exerts a marked disruption of those homeostatic mechanisms whose efficiency represents the essential prerequisite to face the challenges of the interstitial environment. [source] Preparation and cytotoxic properties of goethite-based nanoparticles covered with decyldimethyl(dimethylaminoethoxy) silane methiodideAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 3 2010Izolda Segal Abstract The present work describes the synthesis, physico-chemical and biological properties of the first water-soluble goethite nanoparticles covered with biologically active components: oleic acid and cytotoxic decyldimethyl(dimethylaminoethoxy)silane methiodide. The structure of initial goethite nanoparticles synthesized was proved by XRD analysis and the rough estimation of nanoparticles core size gave the value of 8 nm. The size of colloidal water-soluble nanoparticles, determined by dynamic light scattering, was within 19,35 nm. Magnetic properties and cytotoxicity (against HT-1080 and MG-22A tumor cell lines) of the nanoparticles obtained were investigated. Copyright © 2009 John Wiley & Sons, Ltd. [source] Synthesis and Structure-Activity Relationship Studies of Pyrazole-based Heterocycles as Antitumor AgentsARCHIV DER PHARMAZIE, Issue 7 2010Ahmad M. Farag Abstract Several 4-cyano-1,5-diphenylpyrazoles attached to different heterocyclic ring systems at position 3 were synthesized starting from ethyl 4-cyano-1,5-diphenyl-1H -pyrazole-3-carboxylate 1. The newly synthesized compounds were tested in vivo for their anti-estrogenic effects and evaluated in vitro for their cytotoxic properties against estrogen-dependent tumors. 3-(5-Mercapto-1,3,4-oxadiazole-2-yl)-1,5-diphenyl-1H -pyrazole-4-carbonitrile 13 revealed the highest cytotoxic activity with a GI50 value equal to 40 nM against the IGROVI ovarian tumor cell line. It also showed an anti-estrogen activity 1.6 more effective than the reference drug, in addition to a high tolerable dose. 3-(5-(Methylthio)-4-phenyl-4H -1,2,4-triazol-3-yl)-1,5-diphenyl-1H -pyrazole-4-carbonitrile 7 was found to have the highest anti-estrogenic activity, while 1,5-diphenyl-3-[5-(phenylamino)-1,3,4-thiadiazol-2-yl]-1H -pyrazole-4-carbonitrile 11 showed the lowest activity. The oral LD50 values revealed that most of the tested compounds are relatively nontoxic. [source] Synthesis, in-vitro Antimicrobial and Cytotoxic Studies of Novel Azetidinone DerivativesARCHIV DER PHARMAZIE, Issue 4 2010Rangappa S. Keri Abstract Developing novel antimicrobial drugs is increasingly important in the modern pharmaceutical industry. A series of novel 3-chloro-4-[4-(2-oxo-2H -chromen-4-ylmethoxy)phenyl]-1-phenylazetidin-2-ones 5a,o have been synthesized from 4-bromomethylcoumarins 1a,e and 4-aryliminomethyl-phenols 3a,c. These compounds were screened for their in-vitro antibacterial activity against two Gram-positive (Staphylococcus aureus and Vancomycin resistant enteroccoccus) and two Gram-negative (Escherichia coli and Shigella dysentery) bacterial strains and antifungal activity against Aspergillus fumigatus, Candida albicans, and Penicillium. Results revealed that compounds 5c, 5f, 5h, 5j, and 5m showed excellent activity against a panel of microorganisms. The brine-shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and two compounds, 5h and 5m, possessing LD50 = 7.154×10,4 M and 5.782×10,4 M, respectively, displayed potent cytotoxic activity against Artemia salina. The presence of a chlorine group in the coumarin moiety, its effect on their antibacterial, antifungal, and cytotoxic activities is discussed. All newly synthesized compounds were characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, and MS. [source] Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cellsCELL PROLIFERATION, Issue 6 2008M. R. Loizzo Materials and methods: Essential oils were obtained by hydrodistillation and were analysed by gas chromatography and gas chromatography coupled to mass spectrometry. Antiproliferative activity was tested on amelanotic melanoma C32 cells and on renal cell adenocarcinoma cells, using the sulphorhodamine B assay. Results: Cupressus sempervirens ssp. pyramidalis leaf oil exerted the highest cytotoxic activity with an IC50 value of 104.90 µg/mL against C32, followed by activity of P. orientalis and P. asperula on the renal adenocarcinoma cell line (IC50 of 121.93 and 139.17 µg/mL, respectively). P. orientalis essential oil was also active against amelanotic melanoma with an IC50 of 330.04 µg/mL. Three identified terpenes, linalool, ,-caryophyllene and ,-cedrol, were found to be active on both cell lines tested. Conclusions: Our findings provide novel insights into the field of cytotoxic properties of essential oils. This study provided evidence on how cytotoxic activity of the oils is not always related to their major constituents, except for lower activity found in both cell lines for ,-cedrol. Interestingly, ,-caryophyllene and linalool exhibited comparable IC50 values to the commercial drug vinblastine on the ACHN cell line. This opens a new field of investigation to discover mechanisms responsible for the observed activity. [source] Labdane Diterpenoid Glycosides from Aster veitchianusCHEMISTRY & BIODIVERSITY, Issue 3 2007Er-Wei Li Abstract Four new labdane-type rhamnopyranosides derived from 13-epimanool, compounds 1,4, with differently acetylated sugar moieties, were isolated from A. veitchianus. Their structures and absolute configurations were elucidated by chemical transformation, spectroscopic and mass-spectrometric analyses (IR, 1D- and 2D-NMR, HR-ESI-MS), as well as by single-crystal X-ray diffraction (compound 1). The isolates 2,4 were investigated for their cytotoxic properties against cultured human hepatoma (SMMC-7721), ovarian neoplasm (HO-8910), and leukemia (HL-60) cells, and for their antibacterial activities against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. [source] The Presence of a Ferrocenyl Unit on an Estrogenic Molecule is Not Always Sufficient to Generate in,vitro CytotoxicityCHEMMEDCHEM, Issue 11 2006Anne Vessičres Dr. Abstract We recently reported the dual (antihormonal and cytotoxic) functionality of ferrocifens, which are organometallic complexes derived from hydroxytamoxifen, the standard molecule in the treatment of hormone-dependent breast cancers. To test the hypothesis that the presence of a ferrocenyl substituent on molecules with an affinity for the estrogen receptor is sufficient to give them cytotoxic properties in,vitro, we prepared complexes derived from estradiol with a ferrocenyl substituent at positions 7, and 17,. The complexes thus obtained retain a satisfactory level of affinity for the estrogen receptor (RBA values higher than 12,%). At low concentrations (0.1,1,,M) the complexes show an estrogenic effect in,vitro equivalent to that of estradiol on hormone-dependent (MCF-7) breast cancer cells, and no cytotoxic effect on hormone-independent (MDA-MB-231) breast cancer cells. At high concentrations (up to 50,,M) the 17, -ethynylferrocenyl estradiol and 7, -ferrocenylmethylthio estradiol become cytotoxic (IC50=13.2,,M and 18.8,,m, respectively) while the 17, -ferrocenylestradiol remains non toxic. The low toxicity of these compounds support our hypothesis that electronic communication between the ferrocenyl and phenol moieties in the hydroxyferrocifens series is a key parameter in the generation of cytotoxic effects at submicromolar concentrations. [source] | |||||||||||||||||||||||||