Philippe Cotelle

Philippe Cotelle
Université de Lille · Centre de Recherche Jean Pierre Aubert (U1172)

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121
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2,301
Citations
Citations since 2017
15 Research Items
890 Citations
2017201820192020202120222023050100150
2017201820192020202120222023050100150
2017201820192020202120222023050100150
2017201820192020202120222023050100150

Publications

Publications (121)
Article
Full-text available
The Hippo pathway consists of a cascade of kinases that controls the phosphorylation of the co-activators YAP/TAZ. When unphosphorylated, YAP and TAZ translocate into the nucleus, where they mainly bind to the TEAD transcription factor family and activate genes related to cell proliferation and survival. In this way, the inhibition of the Hippo pat...
Article
Introduction: The Hippo pathway represents a new opportunity for the treatment of cancer. Overexpression of Yes-associated protein (YAP) or transcriptional coactivator with PDZ-binding motif (TAZ) or TEAD has been demonstrated in cancers and YAP is known to mediate resistance to cancer drugs. Since 2018, the potential of this pathway has been illu...
Article
Viral exoribonucleases are uncommon in the world of RNA viruses. To date, they have only been identified in the Arenaviridae and the Coronaviridae families. The exoribonucleases of these viruses play a crucial role in the pathogenicity and interplay with host innate immune response. Moreover, coronaviruses exoribonuclease is also involved in a proo...
Article
Full-text available
The risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a no...
Article
The Hippo pathway is involved in organ size control and tissue homeostasis by regulating cell growth, proliferation and apoptosis. It controls the phosphorylation of the transcription co-activator YAP (Yes associated protein) and TAZ (Transcriptional coactivator with PDZ-binding motif) in order to control their nuclear import and their interaction...
Article
Starting from our previously reported hit, a series of 1,5‐diaryl‐1,2,3‐triazole‐4‐carbohydrazones was synthesized and evaluated as inhibitors of the YAP/TAZ‐TEAD complex. Binding to hTEAD2 of our compounds was evidenced by nanodifferential scanning fluorimetry and they were also shown by polarization fluorescence to disrupt to some extent YAP‐TEAD...
Article
Arenaviridae is a viral family whose members are associated with rodent-transmitted infections to humans responsible of severe diseases. The current lack of a vaccine and limited therapeutic options make the development of efficacious drugs of high priority. The cap-snatching mechanism of transcription of Arenavirus performed by the endonuclease do...
Article
Full-text available
Intrinsically disordered protein YAP (yes-associated protein) interacts with TEADs transcriptional factors family (transcriptional enhancer associated domain) creating three interfaces. Interface 3, between the Ω-loop of YAP and a shallow pocket of TEAD was identified as the most important TEAD zone for YAP-TEAD interaction. Using the first X-ray s...
Article
Full-text available
Porphyrin derivatives, and in particular Verteporfin (VP), a photosensitizer initially designed for cancer therapy, have been identified as inhibitors of YAP-TEAD interaction and transcriptional activity. We herein report the efficient convergent synthesis of the dipyrrin western half-part of protoporphyrin IX dimethyl ester (PPIX-DME) where the se...
Article
Full-text available
Background: Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost simultaneously as a YAP/TEAD and an autophagosome inhibitor. Over the last past years, YAP (and TAZ), the downstream effectors of the Hippo pathway, have emerged as a promising a...
Article
Herein, we report further insight into the biological activities displayed by the 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) scaffold. Previous studies have evidenced the marked fruitful effect of substitution of this two-metal binding pharmacophore at position 4 by phenyl and benzyl carboxamido chains. Strong human immunodeficiency virus type 1...
Article
Full-text available
Introduction: Integration of the viral genome into the host cell chromatin is a central step in the replication cycle of HIV. Blocking the viral integrase (IN) enzyme therefore provides an attractive therapeutic strategy, as evidenced by the recent clinical approval of three IN strand transfer inhibitors. Dolutegravir is a therapy that is unique in...
Article
Nucleos(t)ide analog drugs profoundly suppress Hepatitis B Virus (HBV) replication but rarely cure the infection, so therapy is usually life-long. The nucleos(t)ide analogs inhibit the viral DNA polymerase and often push HBV to the brink of extinction, so it may be possible to eradicate HBV by suppressing HBV replication further. The HBV ribonuclea...
Article
We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs). Substitution of the N-hydroxyimide two-metal binding pharmacophore at position 4 by carboxamido sidechains was previously shown by us to be fruitful for this scaffold, since strong human immunodeficiency virus typ...
Article
A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect...
Article
Full-text available
Clinical HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) potently inhibit viral replication with a dramatic drop in viral load. However, the emergence of resistance to these drugs underscores the need to develop next-generation IN catalytic site inhibitors with improved resistance profiles. Here, we present a novel candidate IN inhibitor;...
Article
Caffeic acid derivatives are increasingly regarded as potential oncoprotective that could inhibit both the initiation and progression of cancer. Here we have synthesized seven 1-arylnaphthalene lignans and related compounds and tested their impact on breast cancer cell growth in tissue culture. The product of the oxidative dimerization of methyl ca...
Patent
Full-text available
The invention relates to 2-hydroxyisoquinoline-1,3(2H,4H)-diones and related compds. of formula I and II, which are HIV integrase inhibitors and which are useful in the treatment of HIV infection and AIDS. Compds. of formula I and II wherein R1 and R2 are independently H, halo, OH, SH, etc.; R1R2 taken together to form a bivalent radical (CH2)3-5;...
Article
Since the discovery of raltegravir, the first FDA-approved integrase inhibitor, Merck and other pharmaceutical companies have continued their research programs in order to introduce novel molecules as second generation integrase inhibitors. Elvitegravir (Japan Tobacco/Gilead) and dolutegravir (Shionogi/GlaxoSmithKline) are in advanced stages of cli...
Article
2-Hydroxyisoquinoline-1,3(2H,4H)-dione was recently discovered as a scaffold for the inhibition of HIV-1 integrase and the ribonuclease H function of HIV-1 reverse transcriptase. First, we investigate its interaction with Mg(2+) and Mn(2+) using different spectroscopic techniques and report that 2-hydroxyisoquinoline-1,3(2H,4H)-dione forms a 1:1 co...
Article
We report herein the synthesis of a series of fifteen 2-hydroxyisoquinoline-1,3(2H,4H)-dione derivatives. Alkyl and arylalkyl groups were introduced on position 4 of the basis scaffold. All the compounds presented poor inhibitory properties against HIV-1 reverse transcriptase ribonuclease H (RNase H). Four compounds inhibited HIV-1 integrase at a l...
Article
Tau isoforms constitute a family of microtubule-associated proteins that are mainly expressed in neurons of the central nervous system. They promote the assembly of tubulin monomers into microtubules and modulate their stability, thus playing a key structural role in the distal portion of axons. In Alzheimer's disease and related tauopathies, Tau a...
Article
A series of 13 hydroxylated 2-arylnaphthalenes have been synthesized and evaluated as HIV-1 integrase inhibitors. 7-(3,4,5-trihydroxyphenyl)naphthalene-1,2,3-triol 1c revealed chemical instability upon storage, leading to the isolation of a dimer 5c which was also tested. In the 2-arylnaphthalene series, all compounds were active against HIV-1 IN w...
Article
Aldose reductase (ALR2) of the polyol metabolic pathway is a target enzyme for the treatment of diabetic complications. A variety of synthetic and natural compounds have been observed to inhibit aldose reductase. Among them, rosmarinic acid has been shown to be in vitro an aldose reductase inhibitor in a micromolar range. In this study, two nitro d...
Article
A series of 4-methoxycarbonylisoquinoline-1, 3-diones was obtained from homophthalic acid in four steps. The key step was the quantitative and rapid alkaline cyclization of 2-methoxycarbonyl-2-(2-methoxycarbonylphenyl) acetamides. Homologation easily afforded in the same conditions 5-carboxy-2-benzazepine-1,3-dione.
Article
Since the discovery of MK-0518 (raltegravir, the first FDA-approved integrase inhibitor) in October 2007, Merck Co. researchers have continued to patent original new heterocycles related to raltegravir as powerful strand transfer inhibitors. Among the most recent patented works hexahydrodiazocino-naphthyridinetriones present the particularity to po...
Article
Full-text available
We report herein the synthesis of a series of 19 2-hydroxyisoquinoline-1,3(2H,4H)-dione derivatives variously substituted at position 7 aimed at inhibiting selectively two-metal ion catalytic active sites. The compounds were tested against HIV-1 reverse transcriptase (RT) polymerase, HIV-1 RT ribonuclease H (RNase H), and HIV-1 integrase (IN). Most...
Article
A successful synthesis of fukiic acid is described in 7% overall yield (6 steps from veratraldehyde). rac-Fukiic acid was found to be a potent inhibitor of HIV-1 integrase but did not reveal any antiviral activity in the MT-4 cells assay.
Article
An efficient synthesis of the acid part of salvianolic acid E 2 is described. Compound 2 was obtained from vanillin in 10 steps and 21% overall yield. During the synthesis of 2 an unexpected 5-oxo-4b,9b-dihydroindano[1,2-b]benzofuran rac-12 was isolated. Both compounds together with the acid part of salvianolic acid D were active as HIV-1 integrase...
Article
A series of thirteen 4,5-diaryl-3-hydroxy-2(5H)-furanones were synthesized. They were evaluated for their antioxidant potencies and inhibitory properties of 5-lipoxygenase, cyclooxygenases, HIV-1 integrase and PC3 cell proliferation. New hits were discovered either in the anti-proliferation test or in the HIV anti-integrase test.
Article
Rosmarinic acid was reacted with nitrite ions under acidic conditions to give 6'-nitro- and 6',6''-dinitrorosmarinic acids according to the reaction time. Both compounds were active as HIV-1 integrase inhibitors at the submicromolar level. They also inhibited the viral replication in MT-4 cells with modest and similar selectivity indexes. The nitra...
Article
Following the discovery of diketoacid-containing compounds as HIV-1 integrase (IN) inhibitors, a plethora of new molecules have been published leading to four drugs under clinical trial. In an attempt to rationally design new dimeric diketoacids (DKAs) targeting two divalent metal ions on the active site of IN, potent inhibitors against purified IN...
Article
Full-text available
A successful synthesis of the acid part of salvianolic acid D is described (eight steps from isovanillin, 22% overall yield). The benzaldehyde key intermediate was obtained in six steps in 52% overall yield and was converted into the trimethylated precursor molecule using the Knoevenagel procedure. Finally, the acid part of salvianolic acid D was o...
Article
Full-text available
Combination therapy, comprising at least three anti-human immunodeficiency virus (anti-HIV) drugs, has become the standard treatment of AIDS. Since 1996, highly active antiretroviral therapy (HAART) was designed to rapidly control HIV replication. It has had a significant impact on patient health and progression of AIDS in developed countries but i...
Article
The synthesis of two caffeoyl-coumarin conjugates, derived from sagecoumarin, has been accomplished, starting from ferulic acid, isoferulic acid and sesamol. Both compounds exhibited potent inhibitory activities at micromolar concentrations against HIV-1 integrase in 3'-end processing reaction but were less effective against HIV-1 replication in a...
Article
The acid-treatment of arylpropanoid derivatives may lead to numerous polyphenols presenting a wide variety of biological properties such as anti-inflammatory, anticancer and antiviral activities and may constitute an alternative route to neolignans to the classical oxidative dimerisation of arylpropenoid compounds. Firstly, I will present the acidi...
Article
Full-text available
It is demonstrated that electron-rich disubstituted acetophenones react according to various electrophilic nitration conditions that generally lead to ipso substitution accompanying the conventional reaction. The hydroxy substituent does not seem prone to favor such behaviour.
Article
Methoxylated phenylethanals were treated with concentrated hydrochloric acid in 1,4-dioxane to give methoxylated 2-phenylnaphthalenes or 1,2,9,10-tetrahydro-1,9-epoxydibenzo[a,e]cyclooctenes. Yields in 2-phenylnaphthalenes were quite good and 1,2,9,10-tetrahydro-1,9-epoxydibenzo[a,e]cyclooctenes could be easily isolated. 2-Phenylnaphthalenes were o...
Article
Full-text available
Since 1996, highly active antiretroviral therapy (HAART) was designed to rapidly control HIV replication. It has had a significant impact on patient health and progression of AIDS in developed countries, but its success has not been complete. HAART strategy still suffers from issues of patient compliance, cost, deleterious side effects and emerging...
Article
A series of hydroxylated 3-hydroxycoumarins was synthesised by the reaction of 3-aryl-2-hydroxypropenoic derivatives with boron tribromide. They were evaluated for their ability to scavenge the 2,2-diphenyl-1-picrylhydrazyl radical, the superoxide anion radical, the hydroxyl radical and the peroxynitrite anion and to inhibit copper-induced human LD...
Article
Full-text available
A simple and efficient oxalylation of aryl methyl ketones was accomplished with dimethyl oxalate in the presence of sodium methoxide. The unpreviously reported sodium ketoenolate esters were isolated and gently hydrolyzed into the ketoenol esters in good yields. Alternatively the sodium ketoenolate esters hydrolysis could also be conducted to direc...
Article
Full-text available
The interactions with divalent cations of 4-phenyl-4-oxo-2-hydroxybuten-2-oic acid (benzoylpyruvic acid (BPA)), the pharmacophore of HIV-1 integrase inhibitors, were investigated using spectroscopic tools. In the absence of the enzyme, a 2:2 metal-ligand complex was characterized with an intermetallic distance of 4-6 A. Molecular modeling allowed u...
Article
Two new flavones (1 and 2) in which one or two di-tert-butylhydroxyphenyl groups replace the B-ring of flavonoids, respectively, were synthesized according to the Baker–Vankataraman method. Their crystal structures were determined by x-ray diffraction methods and compared with those obtained by theoretical calculations using join Monte Carlo confor...
Article
Full-text available
HIV-1 integrase is an essential enzyme for retroviral replication. It is involved in the integration of HIV DNA into host chromosomal DNA and appears to have no functional equivalent in human cells. Therefore it is an attractive and rational target for selective anti-AIDS therapy. A great number of HIV-1 integrase inhibitors have been described in...
Article
EPR spectroscopy of 3-hydroxyesculetin (1, solid and in solution) and of the radicals formed during the aerobic oxidation of alkaline solutions of 1 and related compounds was investigated. 1 in the solid state was studied by pulsed EPR experiments and showed a radical character. The aerobic oxidation of alkaline solutions of 1 was also followed by...
Article
4-(4-Hydroxyphenyl)-5-(4-hydroxyphenylmethyl)-2-hydroxyfurane-2-one 1 was prepared by an acidic dimerisation of 4-hydroxyphenylpyruvic acid and some of its antioxidant and spectroscopic properties have been measured and compared to that of ascorbic acid. 1 is as good an antioxidant as ascorbic acid in the DPPH (2,2-diphenyl-1-picryl hydrazyl radica...
Article
Methyl isoferulate reacts with FeCl3 to give (2-6) dimer 3 (6-6) dimer 4 and (6-O-3) dimer 5 in low yields, whereas it reacts with Ag2O leading to (2-O-3) dimer 6 and (6-O-3, 2-O-3) trimer 7. By comparison with literature data, we suggest that the biosynthesis of lithospermic acids and related nor and neolignans that possess a β-2 bond may be due t...
Article
Full-text available
Fourteen catechol and bis-catechol derivatives have been synthesised and tested for their HIV-1 inhibitory activities. The six more active molecules have been tested for their antiviral activity and cytotoxicity. We have found that bis-catechols 1 and 2 are the most active HIV-1 integrase inhibitor whereas the best antiviral compound is 4.
Article
The chrome derivatives can be obtained in excellent yields, in three steps, using first the phase transfer catalysis for the synthesis of phenol ether followed by cyclization and the Perkin reaction
Article
The prenylated cinnamic acids can be obtained in excellent yields, in two steps, using first a one-step conversion of corresponding bromobenzaldehydes to corresponding prenylated benzaldehydes
Article
An expeditious synthesis of polyhydroxylated 2-arylbenzo[b]furans is described. The key steps are the conversion of the corresponding polymethoxylated stilbenes into diarylethanoid molecules (epoxide or alcohol) that were demethylated and cyclised using boron tribromide to give the target polyhydroxylated 2-arylbenzo[b]furans.
Article
Cited By (since 1996): 24, Export Date: 31 July 2012, Source: Scopus
Article
Three polyhydroxy-2-phenylnaphthalenes (1-3) and the oxy analogue of tetrahydroxypavinan (4) were prepared and evaluated for their antioxidant properties (inhibition of diphenylpycrylhydrazyl radical (DPPH), reduction of iron (III) ion) and inhibition of 5-lipoxygenase (5-LO) activity. Their three-dimensional structures were established on the basi...
Article
(Z)-Mono, di or trimethoxyphenyl-2-hydroxypropenoic acids 1a–d gave mixtures of (E) and (Z) mono, di or trihydroxyphenyl-2-hydroxypropenoic acids 2a–d when treated with boron tribromide. The isomerisation proceeds during the work-up and depends on the duration of the hydrolysis and the number of oxygens on the aromatic ring. When the aromatic ring...
Article
The synthesis and spectroscopic properties of the three isomers of nitrocaffeic acid are described. The three pKa s of each isomer were measured by UV–visible spectroscopy. The comparison of the UV–visible spectra of nitrocaffeic acids and those obtained from the reaction of caffeic acid with reactive nitrogen species led to the conclusion that the...
Article
Treatment of arylacetones 1 with boron tribromide gives 1,3-dimethyl-2- arylnaphthalenes 3 in fair to good yields by a tandem aldol condensation- intramolecular cyclization. This reaction is limited to the electron-rich arylacetones. In the case of methoxyphenylacetones, a demethylation occurs leading to 1,3-dimethyl-2-hydroxyphenylnaphthols. Other...
Article
An expeditious synthesis of salvianolic acid F 2 is described in 10% overall yield. Tetramethyl salvianolic acid F 3 was obtained in six steps in 39% overall yield and was converted into the target molecule using boron tribromide in 26% yield.
Article
Treatment of electron-rich aromatic derivatives with cerium (IV) ammonium nitrate coated on silica (CAN/Si02) affords nitro aromatic compounds. The scope and the limitation of this reaction are discussed.
Article
The reaction of tetramethylsalvianolic acid F 3 with BBr3 led to the expected salvianolic acid F 2 in 10% yield. 2 underwent Diels-Alder cyclisation to 5 or cyclisation to benzofuran 6 depending on the reaction conditions.
Article
Treatment of arylethanals 1 with boron tribromide give 2-phenylnaphthalenes 2 or 1,2,9,10-tetrahydro-1,9-epoxydibenzo[a,e]cyclooctenes 3 by a tandem aldol condensation-intramolecular Friedel-Crafts cyclization or a condensation at the O-position followed by a double Friedel-Crafts alkylation respectively. In all cases, a total demethylation of the...
Article
Treatment of phenylacetones 1 with boron tribromide gives the 1,3-dimethyl-2-phenylnaphtalenes 2 in good yields by a tandem aldol condensation-intramolecular Friedel-Crafts cyclization. In the cases of methoxyphenylacetones, a demethylation occurs leading to 1,3-dimethyl-2-hydroxyphenylnaphtols. © 1997 Published by Elsevier Science Ltd.
Article
α-hydroxyesters 5a-g or diols 6a-g have been obtained in high yields by reduction of aromatic α-ketoesters 4 once or twice respectively by using NaBH4 as the reducer under suitable conditions. The use of a solvent that does not interact with the reagent allowed the double reduction to occur with only a slight excess of borohydride in very mild cond...
Article
Five peptides related to the N-terminal sequence of the vasoactive intestinal peptide (VIP) have been synthesized. Two-dimensional nuclear magnetic resonance (2D-NMR) experiments (i.e., correlated spectroscopy [COSY]) and low temperature coefficient measurements for particular NH chemical shifts suggest the presence of hydrogen bondings in both VIP...
Article
The nitration ipso to a carboxylic or formyl group of disubstituted and trisubstituted benzoic acids and benzaldehydes using nitric acid in acetic acid is described.
Article
The oxidation behaviour of gentisic acid, from which a humic acid model was synthesized, was studied. Electrochemical investigation coupled with Electron Spin Resonance analysis revealed the complexity of the mechanism. Coupled chemical reactions appeared after the two electron oxidation, leading to trihydroxybenzoic acids, and to dimeric compounds...
Article
A series of nitrodihydroxybenzenes and nitrocaffeic acids were prepared and their hydroxyl radical (OH°) and superoxide anion (O2−) scavenging activities and xanthine oxidase inhibition activities were evaluated. 2-Nitrocaffeic acid is the more potent O2− scavenger. 2- (and 5)-Nitrocaffeic acids are the more potent xanthine oxidase inhibitors.
Article
A mild and efficient method for the synthesis of 3, 4-dihydroisoquinolinium salts, key intermediates for the preparation of isoquinoline alkaloïds, by an oxidation of N-methyl-1, 2, 3, 4-tetrahydroisoquinolines using ceric ammonium nitrate (CAN) is described.
Article
The oxidative cleavage of 2,5-dihydroxybenzoic acid (gentisic acid), presumably into maleylpyruvate in basic aqueous solution has been shown by ESR spectra of semiquinonic radicals bearing a methylenic group. One of these radicals has been unambiguously attributed to 2,4,5-trihydroxyphenylacetic acid semiquinonic radical. The formation of an hydrox...
Article
Les nitrocatechols et la nitrohydroquinone ont ete traitees par le borohydrure de sodium en solution basique oxygenee a des pH allant de 9 a 12 et leur spectre RPE a ete enregistre. Dans tous les cas le radical anion nitroaromatique est observe. A pH 12 un radical semiquinonique a ete observe dans le cas de la nitrohydroquinone et du 4-nitrocatecho...
Article
The isolation and characterization is described of four novel cyclic polyethers, bistramides B [2], C [3], D [4], and K [5], which are closely related to the previously reported bistramide A [1] from the New Caledonian urochordata Lissoclinum bistratum. The structures of these metabolites were defined by spectroscopic methods. The four compounds ex...
Article
N,N-Dimethylmethoxyphenylmethylamines were selectively converted to the corresponding methoxybenzaldehydes using Ceric Ammonium Nitrate (CAN) in acetonitrile/water.