Publications by authors named "Candice Botuha"

13 Publications

  • Page 1 of 1

Insights into the antiproliferative mechanism of (C^N)-chelated half-sandwich iridium complexes.

Dalton Trans 2020 Dec;49(48):17635-17641

Institut Parisien de Chimie Moléculaire (IPCM), Sorbonne Université, CNRS, 4 place Jussieu, F-75005 Paris, France.

Transition metal-based anticancer compounds, as an alternative to platinum derivatives, are raising scientific interest as they may present distinct although poorly understood mechanisms of action. We used a structure-activity relationship-based methodology to investigate the chemical and biological features of a series of ten (C^N)-chelated half-sandwich iridiumIII complexes of the general formula [IrCp*(phox)Cl], where (phox) is a 2-phenyloxazoline ligand forming a 5-membered metallacycle. This series of compounds undergoes a fast exchange of their chlorido ligand once solubilised in DMSO. They were cytotoxic to HeLa cells with IC50 values in the micromolar range and induced a rapid activation of caspase-3, an apoptosis marker. In vitro, the oxidative power of all the complexes towards NADH was highlighted but only the complexes bearing substituents on the oxazoline ring were able to produce H2O2 at the micromolar range. However, we demonstrated using a powerful HyPer protein redox sensor-based flow cytometry assay that most complexes rapidly raised intracellular levels of H2O2. Hence, this study shows that oxidative stress can partly explain the cytotoxicity of these complexes on the HeLa cell line and gives a first entry to their mechanism of action.
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http://dx.doi.org/10.1039/d0dt03414bDOI Listing
December 2020

A Bis-Chelating / Ligand for the Synthesis of Heterobimetallic Platinum(II)/Rhenium(I) Complexes: Tools for the Optimization of a New Class of Platinum(II) Anticancer Agents.

Chemistry 2020 Oct 11;26(56):12846-12861. Epub 2020 Sep 11.

CNRS, Institut Parisien de Chimie Moléculaire (IPCM), Sorbonne Université, 75005, Paris, France.

The two independent and coordination sites of a newly synthesized bis[2-(hydroxyphenyl)-1,2,4-triazole] platform have been exploited to prepare four monometallic neutral ()Pt complexes carrying DMSO, pyridine, triphenylphosphine, or N-heterocyclic carbene as the fourth ligand. Then, the second coordination site was used to introduce an IR-active rhenium tricarbonyl entity, affording the four corresponding heterobimetallic neutral Pt /Re complexes, as well as a cationic Pt /Re derivative. X-ray crystallographic studies showed that distortion of the organic platform occurred to accommodate the coordination geometry of both metal centers. No ligand exchange or transchelation occurred upon incubation of the Pt complexes in aqueous environment or in the presence of Fe , respectively. The antiproliferative activity of the ligand and complexes was first screened on the triple-negative breast cancer cell line MDA-MB-231. Then, the IC values of the most active candidates were determined on a wider panel of human cancer cells (MDA-MB-231, MCF-7, and A2780), as well as on a nontumorigenic cell line (MCF-10A). Low micromolar activities were reached for the complexes carrying a DMSO ligand, making them the first examples of highly active, but hydrolytically stable, Pt complexes. Finally, the characteristic mid-IR signature of the {Re(CO) } fragment in the Pt/Re heterobimetallic complexes was used to quantify their uptake in breast cancer cells.
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http://dx.doi.org/10.1002/chem.202001752DOI Listing
October 2020

Chiral Dawson-Type Hybrid Polyoxometalate Catalyzes Enantioselective Diels-Alder Reactions.

Chemistry 2015 Nov 25;21(46):16512-6. Epub 2015 Sep 25.

Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UMR 8232, Institut Parisien de Chimie Moléculaire (IPCM), 75005 Paris (France).

Can achiral organocatalysts linked to chiral polyanionic metal oxide clusters provide good selectivity in enantioselective C-C bond formations? The answer to this question is investigated by developing a new active hybrid polyoxometalate-based catalyst for asymmetric Diels-Alder reaction. Chirality transfer from the chiral anionic polyoxometalate to the covalently linked achiral imidazolidinone allows Diels-Alder cycloaddition products to be obtained with good yields and high enantioselectivities when using cyclopentadiene and acrylaldehydes as partners.
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http://dx.doi.org/10.1002/chem.201502839DOI Listing
November 2015

Access to pyridyl-substituted 1,3,5-triazines from 4H-pyrido[1,3]oxazin-4-ones via a cyclocondensation process.

J Org Chem 2014 Jul 1;79(14):6579-89. Epub 2014 Jul 1.

Exploratory Unit, Sanofi R&D , 1 Avenue Pierre Brossolette, 91385 Chilly Mazarin Cedex, France.

Pyridyl-substituted 1,3,5-triazines were synthesized in good to excellent yields via an unprecedented one-step cyclocondensation of 4H-pyrido[1,3]oxazin-4-ones with amidines at room temperature or under microwave irradiations. The broad applicability was demonstrated by 33 examples with a variety of amidines and three different 4H-pyrido[1,3]oxazin-4-one chemical series. In addition, a one-pot process from 4H-pyrido[1,3]oxazin-4-one precursors (imide sodium salts) was developed and led to the desired triazines compounds, thus allowing a one-step economy in their global synthetic preparation. This approach provides rapid access to pyridyl (or pyridone)-substituted 1,3,5-triazines with high potential in various fields of application.
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http://dx.doi.org/10.1021/jo5010668DOI Listing
July 2014

Expeditive access to 2-substituted 4H-pyrido[1,3]oxazin-4-ones via an intramolecular O-arylation.

Org Lett 2013 Jul 5;15(14):3494-7. Epub 2013 Jul 5.

Sanofi R&D, Exploratory Unit, 1 Avenue Pierre Brossolette, 91385 Chilly Mazarin Cedex, France.

Unreported 2-substituted 4H-pyrido[e][1,3]oxazin-4-ones are synthesized via an unprecedented intramolecular O-arylation of N-aroyl- and N-heteroaroyl-(iso)nicotinamides under microwave irradiations, in good to excellent yields. The broad applicability was demonstrated by 24 examples with a variety of substituents at the 2-position of the final compounds and 3 possible positions for the nitrogen atom of the pyridine ring. In addition, transformation of one of these compounds into 2-hydroxypyridyl-substituted 1,2,4-triazole and 1,2,4-oxazinone was realized. This approach opens a rapid access to a new bicyclic heteroaromatic chemical series with high potential in medicinal chemistry.
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http://dx.doi.org/10.1021/ol401516eDOI Listing
July 2013

Cyclization of zincated α-N-homoallylamino nitriles: a new entry to enantiopure 2,3-methanopyrrolidines.

Chemistry 2010 Nov;16(42):12668-77

UPMC Univ Paris 06, UMR CNRS 7201, Institut Parisien de Chimie Moléculaire, Institut de Chimie Moléculaire (FR 2769), Case 183, 4 place Jussieu, 75005 Paris, France.

Stereoselective cyclization of zincated α-N-homoallylamino nitriles has been developed. Following treatment with lithium diisopropylamide (LDA) and transmetalation with zinc bromide, α-N-(1-phenylethyl)-N-homoallylamino nitriles lead to 2,3-methanopyrrolidines in moderate to good yields (up to 66 %) and excellent selectivities (up to >98:2). With substrates derived from α-branched homoallylic amines, a stereospecific inversion of the homoallylic stereogenic center was observed. To account for this, a mechanistic rationale involving the formation of zincioiminium ions from zincated α-amino nitriles is put forward. 2,3-Methanopyrrolidines should then arise from a sequence involving an aza-Cope rearrangement providing a configurationally stable (2-azoniaallyl)zinc species that then undergoes a [3+2] cycloaddition reaction.
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http://dx.doi.org/10.1002/chem.201001639DOI Listing
November 2010

High-yielding synthesis of sphingoid-type bases.

J Org Chem 2009 Sep;74(18):6986-92

UPMC-Univ Paris 06, CNRS UMR 7201, Institut Parisien de Chimie Moléculaire (FR 2769), case 183, 4 place Jussieu, F-75005 Paris, France.

An efficient methodology for the synthesis of sphingoid-type bases is reported. It involves the stereoselective addition of a racemic 3-alkoxy allenylzinc to enantiopure N-tert-butylsulfinyl imines and a cross-metathesis reaction as the key steps. It has been successfully applied to the syntheses of sphinganine and naturally occurring bioactive related compounds, among which the hydrolysis product of clavaminol H and two spisulosines. All of these compounds have been prepared in six steps from N-tert-butylsulfinyl imines in high overall yields (>56%).
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http://dx.doi.org/10.1021/jo901567qDOI Listing
September 2009

tert-Butanesulfinimines: structure, synthesis and synthetic applications.

Chem Soc Rev 2009 Apr 26;38(4):1162-86. Epub 2009 Jan 26.

UPMC Univ Paris 06, UMR 7611, Laboratoire de Chimie Organique, Institut de Chimie Moléculaire (FR 2769), case 183, 4 place Jussieu, F-75005, Paris, France.

Since Ellman's seminal works, over the past ten years tert-butanesulfinimines have proved to be useful chiral amino intermediates for organic synthesis. Through highly stereoselective reactions, amongst which reductions, nucleophilic 1,2-additions and ylide condensations, a broad range of nitrogen-containing compounds has been synthesized. Although the stereoselectivity levels are high in most cases, the sense of the stereoinduction is generally not predictable. The object of this critical review is to present the models proposed to rationalize the stereochemical outcome of the reactions involving tert-butanesulfinimines and to point out an obvious lack of homogeneity amongst them (128 references).
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http://dx.doi.org/10.1039/b809772kDOI Listing
April 2009

New asymmetric synthesis of protein farnesyltransferase inhibitors via palladium-catalyzed cross-coupling reactions of 2-iodo-imidazoles.

Org Biomol Chem 2009 May 6;7(10):2214-22. Epub 2009 Apr 6.

Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherche de Gif-sur-Yvette, Avenue de la Terrasse, 91198 Gif-sur-Yvette cedex, France.

Palladium catalyzed cross-coupling reactions of 2-iodoimidazole have been studied to synthesize imidazole-containing protein farnesyltransferase inhibitors. The Suzuki coupling reaction proved to be very efficient to introduce functionalized alkyl chains at the 2-position of the imidazole ring and a new synthesis of the required alkenylboronates was realised by a reaction of cross metathesis. Asymmetric synthesis of allyl succinic derivatives allowed us to synthesize chiral protein farnesyltransferase inhibitors through Suzuki coupling and to determine the influence of the stereochemistry of our inhibitors on the enzymatic activity.
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http://dx.doi.org/10.1039/b902601kDOI Listing
May 2009

Expeditious synthesis of a common intermediate of L-1-deoxyallonojirimycin and L-1-deoxymannojirimycin.

J Org Chem 2009 Mar;74(5):2238-41

UPMC Univ Paris 06 and CNRS, UMR 7611, Laboratoire de Chimie Organique, Institut de Chimie Moléculaire (FR 2769), case 183, 4 place Jussieu, F-75005 Paris, France.

The expeditious synthesis of a common intermediate of L-1-deoxyallonojirimycin (L-allo-DNJ) and L-1-deoxymannojirimycin (L-manno-DNJ) is reported. This intermediate is obtained in highly diastereo- and enantioselectivity with 38.4% overall yield in six steps involving the unprecedented ring-closing metathesis of a tert-butylsulfinyl allylamine as the key step.
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http://dx.doi.org/10.1021/jo802757fDOI Listing
March 2009

Stereo- and enantioselective synthesis of acetylenic 2-amino-1,3-diol stereotriads.

Org Lett 2009 Feb;11(4):931-4

UPMC Univ Paris 06, UMR7611, Laboratoire de Chimie Organique, Institut de Chimie Moléculaire (FR2769), case 183, 4 place Jussieu, F-75252 Paris Cedex 05, France.

The high-yielding and highly efficient stereoselective synthesis of enantiopure anti,anti and syn,anti acetylenic 2-amino-1,3-diol stereotriads from alpha-alkoxy-tert-butanesulfinylimines bearing a stereocenter alpha to the imino group is reported. The stereoselectivity of the reaction of these tert-butanesulfinyl (tBS)-imines with allenylzinc (+/-)-1 was found to be controlled only by the configuration of the tBS group. An excellent kinetic resolution of the racemic allenylzinc species was observed, allowing a high stereocontrol no matter what the configuration or the protecting group of the alpha-alkoxy group.
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http://dx.doi.org/10.1021/ol802912fDOI Listing
February 2009

Radical-polar crossover domino reaction involving alkynes: a stereoselective zinc atom radical transfer.

Chemistry 2008 ;14(29):8784-8

UPMC University Paris 06, UMR 7611, Laboratoire de Chimie Organique, Institut de Chimie Moléculaire (FR 2769), Case 183, 4 place Jussieu, 75005 Paris, France.

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http://dx.doi.org/10.1002/chem.200801451DOI Listing
December 2008

A short synthesis of (+/-)-cytisine.

Org Biomol Chem 2004 Jul 4;2(13):1825-6. Epub 2004 Jun 4.

School of Chemistry, University of Bristol, Bristol, UKBS8 1TS.

The synthesis of racemic cytisine has been completed using (i)N-selective alkylation of 6-bromopyridone with bromide and (ii) Pd(0) mediated intramolecular alpha-arylation of lactam as key steps to achieve rapid assembly of the tricyclic core skeleton of the lupin alkaloids.
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http://dx.doi.org/10.1039/b405275gDOI Listing
July 2004
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