vincent peyrot | Aix-Marseille University (original) (raw)
Papers by vincent peyrot
Journal of Biological Chemistry, Mar 14, 2010
The invention relates to derivatives of 4 -arylcoumarine and 4 -arylquinoleine as medicament for ... more The invention relates to derivatives of 4 -arylcoumarine and 4 -arylquinoleine as medicament for the treatment of cancer, more particularly for the treatment of testicular cancer, brain and kidney and more particularly related to cancer expression (overexpression ) of P-gp and BCRP. The invention also relates to the method of synthesis of such derivatives of 4-arylcoumarine and 4 -arylquinoleine.
![Research paper thumbnail of Theoretical studies of the ground state and of the spectroscopic properties of ethyl 5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4- b ]pyrazin-7-yl carbamate analogs](https://attachments.academia-assets.com/81345456/thumbnails/1.jpg)
](Journal of Molecular Structure: THEOCHEM
Journal of Molecular Biology
European journal of medicinal chemistry, Jan 23, 2016
Several colchicine analogues in which the N-acetyl residue has been replaced by aliphatic, straig... more Several colchicine analogues in which the N-acetyl residue has been replaced by aliphatic, straight-chain acyl moieties, have been synthesized. These compounds show high cytotoxic activity at the nanomolar level against the tumoral cell lines HT-29, MCF-7 and A549. Some of them exhibit activities in the picomolar range against the HT-29 line and are thus two to three orders of magnitude more cytotoxic than colchicine. In this specific cell line, the activities were found to be closely related to the length of the acyl carbon chain, an increase in the latter giving rise to an increase in the cytotoxicity with a maximum in the range of 10-12 carbon atoms, followed by a decrease in activity with still longer chains. Some of the compounds inhibit microtubule assembly and induce the formation of abnormal polymers and present in most cases better apparent affinity constants than colchicine. In addition, at IC50 concentrations the analogues block the cell cycle of A549 cells in the G2/M ph...
Methods in Molecular Biology, 2016
European journal of pharmacology, Jan 12, 2016
The NADPH oxidase proteins catalyse the formation of superoxide anion which act as signalling mol... more The NADPH oxidase proteins catalyse the formation of superoxide anion which act as signalling molecules in physiological and pathological processes. Nox1-dependent NADPH oxidase is expressed in heart, lung, colon, blood vessels and brain. Different strategies involving Nox1 inhibition based on diphenylene iodonium derivatives are currently tested for colorectal cancer therapy. Here, after peptides screening on Nox1-dependent NADPH oxidase assay in HT-29 cells, we identify a peptide (referred to as NF02), cell-active, that potently block Nox1-dependent reactive oxygen species generation. Study of DEPMPO adduct formation by electron paramagnetic resonance showed that NF02 has no superoxide scavenging activity and no impact on cellular reactive oxygen species-producing enzymes such xanthine oxidase. NF02 was not cytotoxic, inhibited reactive oxygen species production of reconstituted Nox1/Noxo1/Noxa1 complex in HEK293 and did not decrease Nox2 dependent cellular NADPH oxidase reactive ...
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Sep 1, 2016
Stathmin is a prominent destabilizer of microtubules (MTs). Extensive in vitro studies have stron... more Stathmin is a prominent destabilizer of microtubules (MTs). Extensive in vitro studies have strongly suggested that stathmin could act by sequestering tubulin and/or by binding to MT tips. In cells, the molecular mechanisms of stathmin binding to tubulin and/or MTs and its implications for the MT dynamics remain unexplored. By using immunofluorescence resonance energy transfer and fluorescence recovery after photobleaching, we analyzed the ability of stathmin and its phosphorylated forms (on Ser16, -25, -38, and -63) to interact with tubulin and MTs in A549 cells. Consistent with in vitro studies, we detected stathmin-tubulin interactions at the MT plus ends and in the cytosol. Of interest, we also observed a novel pool of stathmin bound along the MT. Expression of truncated stathmin and use of MT-stabilizing taxol further showed that the C-terminal domain of stathmin is the main contributor to this binding and that the phosphorylation state of stathmin plays a role in its binding a...
Molecular biology of the cell, Oct 27, 2016
Proper regulation of microtubule dynamics is essential for cell functions and involves various mi... more Proper regulation of microtubule dynamics is essential for cell functions and involves various microtubule-associated proteins (MAPs). Among them, end-binding proteins (EBs) accumulate at microtubule plus-ends, whereas structural MAPs bind along the microtubule lattice. Recent data indicate that the structural MAP tau modulates EB subcellular localisation in neurons. However the molecular determinants of EB/tau interaction remain unknown, as well as the impact of this interplay on microtubule dynamics. Here, we investigate the mechanisms governing EB/tau interaction in cell-free systems and cellular models. We find that tau inhibits EB tracking at microtubule ends. Tau and EBs form a complex via the C-terminal region of EBs and the microtubule-binding sites of tau. These two domains are required for the inhibitory activity of tau on EB localisation to microtubule ends. Moreover, the phospho-mimetic mutation S262E within tau microtubule-binding sites impairs EB/tau interaction and pr...
AIP Conference Proceedings, 1991
Canadian Journal of Microbiology, 2015
Molecular Pharmacology
We studied the action of E-diethylstilbestrol (E-DES), erythro-hexestrol (erythro-HES), and E,E-d... more We studied the action of E-diethylstilbestrol (E-DES), erythro-hexestrol (erythro-HES), and E,E-dienestrol (E,E-DIES) on microtubule formation. The three drugs inhibit this formation from microtubular protein; the percentages of inhibition were, respectively, 15% and 45% for 1.25 X 10-s M E-DES and E,E-DIES. With purified tubulin 6S, 7.5 X 10(-6) M E,E-DIES and erythro-HES induced a 20% inhibition. In the case of E-DES, our results are in good agreement with previous ones. These drugs partially disrupt preformed microtubules. Moreover, when E,E-DIES (5 X 10(-5) M) is added to tubulin, loosely organized aggregates composed of twisted ribbon structure are formed. In the case of erythro-HES, similar structures were observed but at higher concentrations. With E-DES, no organized structures are present.
International journal of clinical pharmacology, therapy, and toxicology
Disulfiram (Tetraethylthiuram disulfide, DSF) inhibits in vitro tubulin polymerization in a dose-... more Disulfiram (Tetraethylthiuram disulfide, DSF) inhibits in vitro tubulin polymerization in a dose-dependent manner after a preliminary incubation time. Electron micrographs show that microtubules are shorter and less numerous. This inhibition may be correlated to blockade of protein SH groups. The linkage of DSF-tubulin hinders the vinca alkaloids-tubulin binding as shown using radioactive assay and microcalorimetric measurements. These results could be responsible for the occurrence of some side effects observed during the therapeutic use of this drug.
European Journal of Biochemistry
Journal of Biological Chemistry, 2010
Analytical Chemistry, 2015
Journal of Biological Chemistry, Mar 14, 2010
The invention relates to derivatives of 4 -arylcoumarine and 4 -arylquinoleine as medicament for ... more The invention relates to derivatives of 4 -arylcoumarine and 4 -arylquinoleine as medicament for the treatment of cancer, more particularly for the treatment of testicular cancer, brain and kidney and more particularly related to cancer expression (overexpression ) of P-gp and BCRP. The invention also relates to the method of synthesis of such derivatives of 4-arylcoumarine and 4 -arylquinoleine.
Journal of Molecular Structure: THEOCHEM
Journal of Molecular Biology
European journal of medicinal chemistry, Jan 23, 2016
Several colchicine analogues in which the N-acetyl residue has been replaced by aliphatic, straig... more Several colchicine analogues in which the N-acetyl residue has been replaced by aliphatic, straight-chain acyl moieties, have been synthesized. These compounds show high cytotoxic activity at the nanomolar level against the tumoral cell lines HT-29, MCF-7 and A549. Some of them exhibit activities in the picomolar range against the HT-29 line and are thus two to three orders of magnitude more cytotoxic than colchicine. In this specific cell line, the activities were found to be closely related to the length of the acyl carbon chain, an increase in the latter giving rise to an increase in the cytotoxicity with a maximum in the range of 10-12 carbon atoms, followed by a decrease in activity with still longer chains. Some of the compounds inhibit microtubule assembly and induce the formation of abnormal polymers and present in most cases better apparent affinity constants than colchicine. In addition, at IC50 concentrations the analogues block the cell cycle of A549 cells in the G2/M ph...
Methods in Molecular Biology, 2016
European journal of pharmacology, Jan 12, 2016
The NADPH oxidase proteins catalyse the formation of superoxide anion which act as signalling mol... more The NADPH oxidase proteins catalyse the formation of superoxide anion which act as signalling molecules in physiological and pathological processes. Nox1-dependent NADPH oxidase is expressed in heart, lung, colon, blood vessels and brain. Different strategies involving Nox1 inhibition based on diphenylene iodonium derivatives are currently tested for colorectal cancer therapy. Here, after peptides screening on Nox1-dependent NADPH oxidase assay in HT-29 cells, we identify a peptide (referred to as NF02), cell-active, that potently block Nox1-dependent reactive oxygen species generation. Study of DEPMPO adduct formation by electron paramagnetic resonance showed that NF02 has no superoxide scavenging activity and no impact on cellular reactive oxygen species-producing enzymes such xanthine oxidase. NF02 was not cytotoxic, inhibited reactive oxygen species production of reconstituted Nox1/Noxo1/Noxa1 complex in HEK293 and did not decrease Nox2 dependent cellular NADPH oxidase reactive ...
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Sep 1, 2016
Stathmin is a prominent destabilizer of microtubules (MTs). Extensive in vitro studies have stron... more Stathmin is a prominent destabilizer of microtubules (MTs). Extensive in vitro studies have strongly suggested that stathmin could act by sequestering tubulin and/or by binding to MT tips. In cells, the molecular mechanisms of stathmin binding to tubulin and/or MTs and its implications for the MT dynamics remain unexplored. By using immunofluorescence resonance energy transfer and fluorescence recovery after photobleaching, we analyzed the ability of stathmin and its phosphorylated forms (on Ser16, -25, -38, and -63) to interact with tubulin and MTs in A549 cells. Consistent with in vitro studies, we detected stathmin-tubulin interactions at the MT plus ends and in the cytosol. Of interest, we also observed a novel pool of stathmin bound along the MT. Expression of truncated stathmin and use of MT-stabilizing taxol further showed that the C-terminal domain of stathmin is the main contributor to this binding and that the phosphorylation state of stathmin plays a role in its binding a...
Molecular biology of the cell, Oct 27, 2016
Proper regulation of microtubule dynamics is essential for cell functions and involves various mi... more Proper regulation of microtubule dynamics is essential for cell functions and involves various microtubule-associated proteins (MAPs). Among them, end-binding proteins (EBs) accumulate at microtubule plus-ends, whereas structural MAPs bind along the microtubule lattice. Recent data indicate that the structural MAP tau modulates EB subcellular localisation in neurons. However the molecular determinants of EB/tau interaction remain unknown, as well as the impact of this interplay on microtubule dynamics. Here, we investigate the mechanisms governing EB/tau interaction in cell-free systems and cellular models. We find that tau inhibits EB tracking at microtubule ends. Tau and EBs form a complex via the C-terminal region of EBs and the microtubule-binding sites of tau. These two domains are required for the inhibitory activity of tau on EB localisation to microtubule ends. Moreover, the phospho-mimetic mutation S262E within tau microtubule-binding sites impairs EB/tau interaction and pr...
AIP Conference Proceedings, 1991
Canadian Journal of Microbiology, 2015
Molecular Pharmacology
We studied the action of E-diethylstilbestrol (E-DES), erythro-hexestrol (erythro-HES), and E,E-d... more We studied the action of E-diethylstilbestrol (E-DES), erythro-hexestrol (erythro-HES), and E,E-dienestrol (E,E-DIES) on microtubule formation. The three drugs inhibit this formation from microtubular protein; the percentages of inhibition were, respectively, 15% and 45% for 1.25 X 10-s M E-DES and E,E-DIES. With purified tubulin 6S, 7.5 X 10(-6) M E,E-DIES and erythro-HES induced a 20% inhibition. In the case of E-DES, our results are in good agreement with previous ones. These drugs partially disrupt preformed microtubules. Moreover, when E,E-DIES (5 X 10(-5) M) is added to tubulin, loosely organized aggregates composed of twisted ribbon structure are formed. In the case of erythro-HES, similar structures were observed but at higher concentrations. With E-DES, no organized structures are present.
International journal of clinical pharmacology, therapy, and toxicology
Disulfiram (Tetraethylthiuram disulfide, DSF) inhibits in vitro tubulin polymerization in a dose-... more Disulfiram (Tetraethylthiuram disulfide, DSF) inhibits in vitro tubulin polymerization in a dose-dependent manner after a preliminary incubation time. Electron micrographs show that microtubules are shorter and less numerous. This inhibition may be correlated to blockade of protein SH groups. The linkage of DSF-tubulin hinders the vinca alkaloids-tubulin binding as shown using radioactive assay and microcalorimetric measurements. These results could be responsible for the occurrence of some side effects observed during the therapeutic use of this drug.
European Journal of Biochemistry
Journal of Biological Chemistry, 2010
Analytical Chemistry, 2015