Search results for "Isoindoles"

Investigation of Isoindolo[2,1-a] quinoxaline-6-imines as Topoisomerase I Inhibitors with Molecular Modeling Methods

2017

Background: Isoindolo[2,1-alpha] quinoxalines constitute an important class of compounds which demonstrated potent antiproliferative activity against different human tumor cell lines and topoisomerase I inhibitors. In particular, their water soluble imine or iminium salts recently synthesized showed potent growth inhibitory effect on NCI-60 tumor cell line panel and biological studies performed on the most active compounds demonstrated that they cause DNA damage via topoisomerase I poisoning. Objective: Herein, we investigate with molecular modeling methods, the common features responsible for topoisomerase I inhibition of the water-soluble isoindolo[2,1-alpha] quinoxalin-6-imines, by compa…

[1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors

2016

Abstract A series of [1,2]Oxazolo [5,4- e ]isoindoles has been synthesized through a versatile and high yielding sequence. All the new structures showed in the 1 HNMR spectra, the typical signal in the 8.34–8.47 ppm attributable to the H-3 of the [1,2]oxazole moiety. Among all derivatives, methoxy benzyl substituents at positions 3 and 4 or/and 5 were very effective in reducing the growth of different tumor cell lines, including diffuse malignant peritoneal mesothelioma (DMPM), an uncommon and rapidly malignancy poorly responsive to available therapeutic options. The most active compound 6j was found to impair tubulin polymerization, cause cell cycle arrest at G2/M phase and induce apoptosi…

Synthesis of Isoxazole and 1,2,3-Triazole Isoindole Derivatives via Silver- and Copper-Catalyzed 1,3-Dipolar Cycloaddition Reaction.

2016

International audience; The CuI-or Ag 2 CO 3-catalyzed [3+2] cycloaddition of propargyl-substituted dihydroisoindolin-1-one (3) with arylnitrile oxides 1a-d (Ar = Ph, p-MeC 6 H 4 , p-MeOC 6 H 4 , p-ClC 6 H 4) produces in good yields novel 3,5-disubstituted isoxazoles 4 of the ethyl-2-benzyl-3-oxo-1-((3-arylisoxazol-5yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylate type. With aryl azides 2a-d (Ar = Ph, p-MeC 6 H 4 , p-OMeC 6 H 4 , p-ClC 6 H 4), a series of 1,4-disubstituted 1,2,3-triazoles 6 (ethyl-2-benzyl-3-oxo-1-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylates) was obtained. The reactions proceed in a regioselective manner affording exclusively racemic adduc…

ANNELATED ISOINDOLES WITH POTENT ANTITUMOR ACTIVITY

2009

Enhancement of retention predictions in reversed-phase liquid chromatography using reference compounds

2004

Abstract The use of reference compounds to correct errors associated with the preparation of mobile phase is studied, in order to enhance modelling of retention for optimisation purposes in reversed-phase liquid chromatography. The method fits individual retention models for a set of reference compounds, which are present in all injections. In second step, mobile-phase composition is corrected for each chromatogram, according to the fitted models of the reference compounds. The enhanced precision provided by the large number of replicates for the reference compounds is partially propagated to the retention models of the analytes. The approach is assayed in the separation of amino acids, aft…

Pyrano[2,3-e]isoindol-2-ones, new angelicin heteroanalogues

2009

A convenient synthesis of the pyrano[2,3-e]isoindol-2-one ring system, an heteroanalogue of angelicin, is reported. Our synthetic approach consists of the annelation of the pyran ring on the isoindole moiety using 5-dialkylamino- or 5-hydroxymethylene intermediates as building blocks. The photoantiproliferative activity of the new derivatives was studied. Some of them bearing the benzyl group at the 8 position were active with IC(50) in the micromolar range. Cell cytotoxicity involves apoptosis, alteration of cell cycle profile and membrane photodamage.

The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma

2022

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA. Several findings highlighted the ability of some chemotherapeutics to induce immunogenic cell death (ICD), which is defined by the cell surface translocation of Calreticulin (CAL…

Direct subphthalocyanine conjugation to bombesin vs. indirect conjugation to its lipidic nanocarrier

2016

International audience; Bombesin (BBN) was covalently bound to graftable subphthalocyanine (SubPc) or to a cholesterol derivative, a component of a liposome that encapsulates non-graftable SubPc. The latter bioconjugation approach was suitable to address the stability of SubPc and was achieved by copper-free click-chemistry on the outer-face of the liposome. Liposomes were purified (FPLC) and then analyzed in size (outer diameter about 60 nm measured by DLS). In vitro binding studies allowed to determine the IC50 13.9 nM for one component of the liposome, cholesterol, conjugated to BBN. Hence, azido- (or alkynyl-) liposomes give fluorophores with no reactive functional group available on th…

Efficacy of the antioxidant ebselen in experimental uveitis.

1999

Inflammation results in the production of free radicals. In a model of experimental uveitis upon subcutaneous injection of endotoxin to Lewis rats, i.e., endotoxin-induced experimental uveitis (EIU), we have evaluated the status of the antioxidant capacity of ocular tissues. EIU results in a decrease of glutathione (GSH) content and glutathione peroxidase (GPx) activity in whole eye homogenates 24-h after endotoxin administration. Furthermore, an increase in malondialdehyde (MDA) content was observed in these same samples, thus confirming the involvement of oxidative stress in the pathophysiology of the process. In view of the ability of the antioxidant ebselen as GPx enzyme mimic, we teste…

Some aspects of cardiac antioxidant defence: Ebselen (PZ 51) treatment increases glutathione peroxidase activity in the rat heart

1990

Ebselcn (PZ 5 1 : 2-phenyl1.2-benzisoelenazol-3-( 2H)-one 1 is ii synthetic organoselenium compound with anti-inflammatory activity ( I . 21, which exhibits glutathione peroxidase (GSH-Px)-like activity, catalysing the reduction o f hydrogen peroxide as well as other organic peroxides [3-5]. Its antiinflammatory effect may be mediated by either the GSH-Px activity, the inhibition of leukotriene B4 formation [6], the antioxidant capacity, or a combination of all of them. Many attempts have been made to increase the antioxidant capacity of the myocardium, since free radical generation has been demonstrated in ischaemia-reperfusion damage [7, 81; superoxide dismutase (SOD) and catalase have be…