Search results for "heterocyclic"

Anti-inflammatory activity of erycristagallin, a pterocarpene from Erythrina mildbraedii.

2003

Erycristagallin, a pterocarpene isolated from Erythrina mildbraedii, was tested in vitro for its antioxidant properties on the stable 2,2-diphenyl-1-pycryl-hydrazyl (DPPH) free radical and on the arachidonic acid metabolism. In addition, erycristagallin was tested on different experimental models of inflammation, such as the acute and chronic inflammation induced by the application of 12-O-tetradecanoylphorbol 13-acetate (TPA) on mice and the phospholipase A(2)-induced mouse paw oedema test. In the carrageenan-induced mouse paw oedema test, the ethyl acetate extract obtained from E. mildbraedii showed anti-inflammatory activity, and erycristagallin was isolated as the active principle. In v…

Pyrrolo[2,1-d][1,2,3,5]tetrazinones deaza analogues of temozolomide with potent antitumor activity

2000

The title compounds, that hold the deaza skeleton of temozolomide, exhibited potent in vitro antiproliferative activity. An evaluation of such a biological activity indicates that the mode of action of these compounds differs from that of temozolomide and is also mechanistically unrelated to that of any known antitumor drug.

Exploring the Reactivity and Biological Effects of Heteroleptic N-Heterocyclic Carbene Gold(I)- Alkynyl Complexes

2020

With the aim to explore the effects of different organometallic ligands on the reactivity and biological properties of a series of twelve heteroleptic AuI complexes, of general formula [Au(NHC)(alkynyl)] (NHC = benzimidazolylidene or 1,3-dihydroimidazolylidene) were synthesized and characterized by 1H and 13C NMR and elemental analysis, and in some cases also by X-ray diffraction. The compounds were all stable in H2O/DMSO as established by NMR spectroscopy, while they could react with model thiols (EtSH) in the presence of water to undergo ligand-substitution reactions. 1H NMR experiments showed that dissociation of the more labile alkynyl ligand was possible for all compounds, while in the…

Reactive oxygen species (ROS) generation inhibited by aporphine and phenanthrene alkaloids semi-synthesized from natural boldine.

2004

Four phenanthrene and one aporphine alkaloids semi-synthesized from boldine were evaluated for their inhibitory effect on reactive oxygen species (ROS) generation. ROS generation by neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine was inhibited in a concentration dependent manner. Alkaloids exerted similar inhibitory effect in the hypoxanthine-xanthine oxidase system than in stimulated neutrophils, which could be attributed to a direct ROS scavenging activity. None of the alkaloids assayed had any effect on xanthine oxidase activity. Therefore the synthesized alkaloids might constitute an alternative therapy in inflammation disorders in which ROS generation is involved.

The influence of electron delocalization upon the stability and structure of potential N-heterocyclic carbene precursors with 1,3-diaryl-imidazolidin…

2010

Targeting N-heterocyclic carbenes (NHCs) with increased π-acceptor character featuring N-fluorophenyl substituents, the molecular 2-chloro-1,3-bis(fluorophenyl)imidazolidine-4,5-diones (1a–c) were isolated from the condensation of the corresponding formamidine with oxalyl chloride. These formal adducts of NHCs with hydrogen chloride demonstrated reactivity akin to that of alkyl halides: 1,3,1′,3′-tetrakis(2,6-dimethylphenyl)-[2,2′]diimidazolidinyl-4,5,4′,5′-tetraone (2b) was formed via the reductive coupling of 1b, while 1,3-bis(2,6-diisopropylphenyl)-4,5-dioxoimidazolidin-2-yl acetate (3c) was formed as the result of a metathesis reaction with mercury(II) acetate. Chloride abstraction resu…

DESIGN, SYNTHESIS, AND BIOLOGICAL EVALUATION OF NOVEL HETEROCYCLIC DERIVATIVES AS MODULATORS OF B-DNA AND G-QUADRUPLEXES DNA FUNCTIONS

Preparation and Characterization of P2 BCh Ring Systems (Ch=S, Se) and Their Reactivity with N-Heterocyclic Carbenes

2018

Four-membered rings with a P2BCh core (Ch = S, Se) have been synthesized via reaction of phosphinidene chalcogenide (Ar*P=Ch) and phosphaborene (Mes*P=BNR2). The mechanistic pathways towards these rings are explained by detailed computational work that confirmed the preference for the formation of P–P, not P–B, bonded systems, which seems counterintuitive given that both phosphorus atoms contain bulky ligands. The reactivity of the newly synthesized heterocycles, as well as that of the known (RPCh)n rings (n = 2, 3), was probed by the addition of Nheterocyclic carbenes, which revealed that all investigated compounds can act as sources of low-coordinate phosphorus species. peerReviewed

MANOTA: a promising bifunctional chelating agent for copper-64 immunoPET

2017

International audience; Improved bifunctional chelating agents (BFC) are required for copper-64 radiolabelling of monoclonal antibodies (mAbs) under mild conditions to yield stable, target-specific imaging agents. Four different bifunctional chelating agents (BFC) were evaluated for Fab (Fragment antigen binding) conjugation and radiolabelling with copper-64. Two DOTA- (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and two NOTA- (1,4,7-triazacyclononane-1,4,7-triacetic acid) derivatives bearing a p-benzyl-isothiocyanate group were conjugated to Fab-trastuzumab - which targets the HER2/neu receptor - and the average number of chelators attached ranged from 2.4 to 4.3 macrocycles …

Novel heterobimetallic radiotheranostic: preparation, activity, and biodistribution.

2014

A novel Ru(II) (arene) theranostic complex is presented. It is based on a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocycle bearing a triarylphosphine and can be tracked in vivo by using the γ emission of (153) Sm atoms. Notably, the heteroditopic ligand can be selectively metalated with ruthenium at the phosphorus atom despite the presence of other functionalities that are prone to metal coordination. Subsequent labeling with radionuclides such as (153) Sm can then be performed easily. The resulting heterobimetallic complex exhibits favorable solubility and stability properties in biologically relevant media. It also shows in vitro cytotoxicity in line with that expected …

Phosphorylation of cytochromes P450: First discovery of a posttranslational modification of a drug-metabolizing enzyme

2005

Cytochromes P450 (CYP) are important components of xenobiotic-metabolizing monooxygenases (CYP-dependent monooxygenases). Their regulation by induction, most commonly by transcriptional activation, mediated by xenobiotics, normally substrates of the corresponding CYP, is well known and has been widely studied. Our team has discovered an additional important regulation of xenobiotic-metabolizing CYPs pertaining to posttranslational modification by phosphorylation. Individual CYPs are phosphorylated by different protein kinases, leading to CYP isoenzyme-selective changes in the metabolism of individual substrates and consequent drastic changes in the control of genotoxic metabolites. Best stu…