Jacques Dubois - Academia.edu (original) (raw)

Papers by Jacques Dubois

Communications, 1970

Les biographies de Paris-Match DANS LA VITRINE Tandis qu' « un ex-forgeron de Skoda devient le nu... more Les biographies de Paris-Match DANS LA VITRINE Tandis qu' « un ex-forgeron de Skoda devient le numéro 1 de Tchécoslovaquie », « Nixon rend Agnew célèbre en 24 heures » ; « Bambuck est sacré grand champion à Sacramento », cependant qu' « Eric Charden bat Aznavour et Bécaud » et « Fré déric Dard les records » ; si « le nouveau roi de Hollywood est un Noir», « Patricia l'épouse idéale entre à la Maison Blanche » ; au moment où « le Michelin consacre les frères Troisgros » et que brillent « trois étoiles dans le ciel de Roanne », « le met teur en scène du Lauréat se plaint : il a trop de succès ». Qu'importe même qu'Henri Langlois soit limogé, si « les cinéastes manifestent » pour sa plus grande gloire.

Communications, 1970

... tonnerre. Parmi les autres, relevons : la Femme spectacle, Compartiment tueurs, Filles haute ... more ... tonnerre. Parmi les autres, relevons : la Femme spectacle, Compartiment tueurs, Filles haute tension. b) Depuis Victor Hugo et Y Homme qui rit, la substitution d'une relative au déterminatif est devenue commune. Mais alors ...

Talanta, 2007

A new in vitro assay for anthelmintic activity using Caenorhabditis elegans is based on the abili... more A new in vitro assay for anthelmintic activity using Caenorhabditis elegans is based on the ability of 5(6)-carboxyfluorescein diacetate (CFDA) to indicate the worm's viability. It is shown for the first time that the treatment of a suspension of worms with a solution of 5(6)-carboxyfluorescein diacetate (4.2%) for 30min transiently induces fluorescence in dead worms only, allowing a fast and efficient determination of the proportion of dead worms by fluorescence microscopy. The proposed test has been validated using mixtures of populations of living and killed C. elegans and proved to be selective, linear in the range 0-100%, accurate and precise. The suitability of the assay to detect anthelmintic activity was then evaluated by studying the toxicity against C. elegans of a series of known anthelmintic compounds (mebendazole, levamisole, niclosamide, pyrantel, piperazine, and thiabendazole) with various modes of action. The worms were exposed to each drug at two concentrations, 50 and 100microg/ml for piperazine, niclosamide, pyrantel and 5 and 10microg/ml for the others. We observed that, in the tested range of doses, piperazine and niclosamide were only moderately toxic, yielding 13.1 and 17.5% of dead worms; due to their mode of action and/or specificity, the low toxicity of these compounds was as expected. The marked activities of all the other compound fully agree with those described in the literature and obtained by other more laborious techniques. These validation data indicate that the proposed in vitro anthelmintic assay using 5(6)-carboxyfluorescein diacetate allows for sensitive measurement of worm viability.

Journal of Pharmacology and Toxicology, 2008

Journal of Natural Products, 2010

Fifteen Amaryllidaceae alkaloids (1-15) were evaluated for their antiproliferative activities aga... more Fifteen Amaryllidaceae alkaloids (1-15) were evaluated for their antiproliferative activities against six distinct cancer cell lines. Several of these natural products were found to have low micromolar antiproliferative potencies. The log P values of these compounds did not influence their observed activity. When active, the compounds displayed cytostatic, not cytotoxic activity, with the exception of pseudolycorine (3), which exhibited cytotoxic profiles. The active compounds showed similar efficacies toward cancer cells irrespective of whether the cell lines were responsive or resistant to proapoptotic stimuli. Altogether, the data from the present study revealed that lycorine (1), amarbellisine (6), haemanthamine (14), and haemanthidine (15) are potentially useful chemical scaffolds to generate further compounds to combat cancers associated with poor prognoses, especially those naturally resistant to apoptosis, such as glioblastoma, melanoma, non-small-cell lung, and metastatic cancers.

Journal of Medicinal Chemistry, 2009

Twenty-two lycorine-related compounds were investigated for in vitro antitumor activity using fou... more Twenty-two lycorine-related compounds were investigated for in vitro antitumor activity using four cancer cell lines displaying different levels of resistance to proapoptotic stimuli and two cancer cell lines sensitive to proapoptotic stimuli. Lycorine and six of its congeners exhibited potency in the single-digit micromolar range, while no compound appeared more active than lycorine. Lycorine also displayed the highest potential (in vitro) therapeutic ratio, being at least 15 times more active against cancer than normal cells. Our studies also showed that lycorine exerts its in vitro antitumor activity through cytostatic rather than cytotoxic effects. Furthermore, lycorine provided significant therapeutic benefit in mice bearing brain grafts of the B16F10 melanoma model at nontoxic doses. Thus, the results of the current study make lycorine an excellent lead for the generation of compounds able to combat cancers, which are naturally resistant to proapoptotic stimuli, such as glioblastoma, melanoma, non-smallcell-lung cancers, and metastatic cancers, among others.

Free Radical Research, 2002

The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and... more The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and accuracy of methods for measuring 8-oxo-7,8-dihydroguanine (8-oxoGua) or the nucleoside (8-oxodG). On two occasions, participating laboratories received samples of different concentrations of 8-oxodG for analysis. About half the results returned (for 8-oxodG) were within 20% of the median values. Coefficients of variation (for three identical samples) were commonly around 10%. A sample of calf thymus DNA was sent, dry, to all laboratories. Analysis of 8-oxoGua/8-oxodG in this sample was a test of hydrolysis methods. Almost half the reported results were within 20% of the median value, and half obtained a CVof less than 10%. In order to test sensitivity, as well as precision, DNA was treated with photosensitiser and light to introduce increasing amounts of 8-oxoGua and samples were sent to members. Median values calculated from all returned results were 45.6 (untreated), 53.9, 60.4 and 65.6 8-oxoGua/10(6) Gua; only seven laboratories detected the increase over the whole range, while all but one detected a dose response over two concentration intervals. Results in this trial reflect a continuing improvement in precision and accuracy. The next challenge will be the analysis of 8-oxodG in DNA isolated from cells or tissue, where the concentration is much lower than in calf thymus DNA.

European Journal of Medicinal Chemistry, 2010

A series of twenty six 8-hydroxyquinoline substituted amines, structurally related to compounds 2... more A series of twenty six 8-hydroxyquinoline substituted amines, structurally related to compounds 2 and 3, were synthesized to evaluate the effects of structural changes on antitumor activity and understand their mechanism of action. The studies were performed on a wide variety of cancer cell lines within glioma and carcinoma models. The results obtained from chemical models and biological techniques such as microarrays suggest the following hypothesis that a quinone methide intermediate which does not react with DNA but which gives covalent protein thiol adducts. Micro-array analysis showed that the drugs induce the expression of a variety of stress related genes responsible for the cytotoxic and cytostatic effects in carcinoma and glioblastoma cells respectively. The described analogues could represent new promising anti-cancer candidates with specific action mechanisms, targeting accessible thiols from specific proteins and inducing potent anti-cancer effects.

Drug Development and Industrial Pharmacy, 2008

To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic system... more To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic systemic toxicity, as well as time and costs of hospitalizations, it has been thought that monoolein-water gels incorporating gentamicin sulfate could be used as local, bioresorbable,and sustained-release implants. For this purpose, four formulations were examined with regard to their physicochemical and in vitro drug release characteristics. Hot stage microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA),and X-ray diffraction showed cubic liquid crystalline and eutectic structures. The more suitable formulation consisting of 80-15-5%wt/wt monoolein-water-gentamicin sulfate progressively released the antibiotic for a period of 3 weeks without burst effect. Moreover, the content and the release profile of gentamicin sulfate were not significantly changed after storage at 2-6 degrees C for a period of 10 months.

Comptes Rendus Chimie, 2004

OPA is often used as an off-line derivatisation agent for fluorimetric detection in gentamicin an... more OPA is often used as an off-line derivatisation agent for fluorimetric detection in gentamicin analysis. As, in general, electrochemical detection is more sensitive than fluorimetric detection, the analysis of gentamicin as its OPA derivatives by high-performance liquid chromatography and electrochemical detection is proposed. The derivatisation procedure is that described by the European pharmacopoeia. The method allows not only the detection of all major gentamicin congeners C 1 , C 1A , C 2A and C 2 , but also of other minor unidentified components. A full validation of the method is presented and comparison is made with fluorimetric detection. A good linearity is found for the four congeners within the dynamic ranges 1-50 µg ml -1 for electrochemical detection and 4-80 µg ml -1 for fluorimetric detection. Both methods presented good accuracy and fidelity, although electrochemical detection is more sensitive than fluorimetric detection. The electrochemical detection method presented in this work appears to be a good alternative to the fluorimetric and pulsed electrochemical detection methods. To cite this article: I.T. Somé et al., C. R. Chimie 7 (2004). © 2004 Published by Elsevier SAS on behalf of Académie des sciences.

Communication et langages, 1976

Bioorganic & Medicinal Chemistry, 2010

A series of 33 novel divanillates and trivanillates were synthesized and found to possess promisi... more A series of 33 novel divanillates and trivanillates were synthesized and found to possess promising cytostatic rather than cytotoxic properties. Several compounds under study decreased by >50% the activity of Aurora A, B, and C, and WEE1 kinase activity at concentrations <10% of their IC(50) growth inhibitory ones, accounting, at least partly, for their cytostatic effects in cancer cells and to a lesser extent in normal cells. Compounds 6b and 13c represent interesting starting points for the development of cytostatic agents to combat cancers, which are naturally resistant to pro-apoptotic stimuli, including metastatic malignancies.

Communications, 1970

Les biographies de Paris-Match DANS LA VITRINE Tandis qu' « un ex-forgeron de Skoda devient le nu... more Les biographies de Paris-Match DANS LA VITRINE Tandis qu' « un ex-forgeron de Skoda devient le numéro 1 de Tchécoslovaquie », « Nixon rend Agnew célèbre en 24 heures » ; « Bambuck est sacré grand champion à Sacramento », cependant qu' « Eric Charden bat Aznavour et Bécaud » et « Fré déric Dard les records » ; si « le nouveau roi de Hollywood est un Noir», « Patricia l'épouse idéale entre à la Maison Blanche » ; au moment où « le Michelin consacre les frères Troisgros » et que brillent « trois étoiles dans le ciel de Roanne », « le met teur en scène du Lauréat se plaint : il a trop de succès ». Qu'importe même qu'Henri Langlois soit limogé, si « les cinéastes manifestent » pour sa plus grande gloire.

Communications, 1970

... tonnerre. Parmi les autres, relevons : la Femme spectacle, Compartiment tueurs, Filles haute ... more ... tonnerre. Parmi les autres, relevons : la Femme spectacle, Compartiment tueurs, Filles haute tension. b) Depuis Victor Hugo et Y Homme qui rit, la substitution d'une relative au déterminatif est devenue commune. Mais alors ...

Talanta, 2007

A new in vitro assay for anthelmintic activity using Caenorhabditis elegans is based on the abili... more A new in vitro assay for anthelmintic activity using Caenorhabditis elegans is based on the ability of 5(6)-carboxyfluorescein diacetate (CFDA) to indicate the worm's viability. It is shown for the first time that the treatment of a suspension of worms with a solution of 5(6)-carboxyfluorescein diacetate (4.2%) for 30min transiently induces fluorescence in dead worms only, allowing a fast and efficient determination of the proportion of dead worms by fluorescence microscopy. The proposed test has been validated using mixtures of populations of living and killed C. elegans and proved to be selective, linear in the range 0-100%, accurate and precise. The suitability of the assay to detect anthelmintic activity was then evaluated by studying the toxicity against C. elegans of a series of known anthelmintic compounds (mebendazole, levamisole, niclosamide, pyrantel, piperazine, and thiabendazole) with various modes of action. The worms were exposed to each drug at two concentrations, 50 and 100microg/ml for piperazine, niclosamide, pyrantel and 5 and 10microg/ml for the others. We observed that, in the tested range of doses, piperazine and niclosamide were only moderately toxic, yielding 13.1 and 17.5% of dead worms; due to their mode of action and/or specificity, the low toxicity of these compounds was as expected. The marked activities of all the other compound fully agree with those described in the literature and obtained by other more laborious techniques. These validation data indicate that the proposed in vitro anthelmintic assay using 5(6)-carboxyfluorescein diacetate allows for sensitive measurement of worm viability.

Journal of Pharmacology and Toxicology, 2008

Journal of Natural Products, 2010

Fifteen Amaryllidaceae alkaloids (1-15) were evaluated for their antiproliferative activities aga... more Fifteen Amaryllidaceae alkaloids (1-15) were evaluated for their antiproliferative activities against six distinct cancer cell lines. Several of these natural products were found to have low micromolar antiproliferative potencies. The log P values of these compounds did not influence their observed activity. When active, the compounds displayed cytostatic, not cytotoxic activity, with the exception of pseudolycorine (3), which exhibited cytotoxic profiles. The active compounds showed similar efficacies toward cancer cells irrespective of whether the cell lines were responsive or resistant to proapoptotic stimuli. Altogether, the data from the present study revealed that lycorine (1), amarbellisine (6), haemanthamine (14), and haemanthidine (15) are potentially useful chemical scaffolds to generate further compounds to combat cancers associated with poor prognoses, especially those naturally resistant to apoptosis, such as glioblastoma, melanoma, non-small-cell lung, and metastatic cancers.

Journal of Medicinal Chemistry, 2009

Twenty-two lycorine-related compounds were investigated for in vitro antitumor activity using fou... more Twenty-two lycorine-related compounds were investigated for in vitro antitumor activity using four cancer cell lines displaying different levels of resistance to proapoptotic stimuli and two cancer cell lines sensitive to proapoptotic stimuli. Lycorine and six of its congeners exhibited potency in the single-digit micromolar range, while no compound appeared more active than lycorine. Lycorine also displayed the highest potential (in vitro) therapeutic ratio, being at least 15 times more active against cancer than normal cells. Our studies also showed that lycorine exerts its in vitro antitumor activity through cytostatic rather than cytotoxic effects. Furthermore, lycorine provided significant therapeutic benefit in mice bearing brain grafts of the B16F10 melanoma model at nontoxic doses. Thus, the results of the current study make lycorine an excellent lead for the generation of compounds able to combat cancers, which are naturally resistant to proapoptotic stimuli, such as glioblastoma, melanoma, non-smallcell-lung cancers, and metastatic cancers, among others.

Free Radical Research, 2002

The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and... more The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and accuracy of methods for measuring 8-oxo-7,8-dihydroguanine (8-oxoGua) or the nucleoside (8-oxodG). On two occasions, participating laboratories received samples of different concentrations of 8-oxodG for analysis. About half the results returned (for 8-oxodG) were within 20% of the median values. Coefficients of variation (for three identical samples) were commonly around 10%. A sample of calf thymus DNA was sent, dry, to all laboratories. Analysis of 8-oxoGua/8-oxodG in this sample was a test of hydrolysis methods. Almost half the reported results were within 20% of the median value, and half obtained a CVof less than 10%. In order to test sensitivity, as well as precision, DNA was treated with photosensitiser and light to introduce increasing amounts of 8-oxoGua and samples were sent to members. Median values calculated from all returned results were 45.6 (untreated), 53.9, 60.4 and 65.6 8-oxoGua/10(6) Gua; only seven laboratories detected the increase over the whole range, while all but one detected a dose response over two concentration intervals. Results in this trial reflect a continuing improvement in precision and accuracy. The next challenge will be the analysis of 8-oxodG in DNA isolated from cells or tissue, where the concentration is much lower than in calf thymus DNA.

European Journal of Medicinal Chemistry, 2010

A series of twenty six 8-hydroxyquinoline substituted amines, structurally related to compounds 2... more A series of twenty six 8-hydroxyquinoline substituted amines, structurally related to compounds 2 and 3, were synthesized to evaluate the effects of structural changes on antitumor activity and understand their mechanism of action. The studies were performed on a wide variety of cancer cell lines within glioma and carcinoma models. The results obtained from chemical models and biological techniques such as microarrays suggest the following hypothesis that a quinone methide intermediate which does not react with DNA but which gives covalent protein thiol adducts. Micro-array analysis showed that the drugs induce the expression of a variety of stress related genes responsible for the cytotoxic and cytostatic effects in carcinoma and glioblastoma cells respectively. The described analogues could represent new promising anti-cancer candidates with specific action mechanisms, targeting accessible thiols from specific proteins and inducing potent anti-cancer effects.

Drug Development and Industrial Pharmacy, 2008

To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic system... more To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic systemic toxicity, as well as time and costs of hospitalizations, it has been thought that monoolein-water gels incorporating gentamicin sulfate could be used as local, bioresorbable,and sustained-release implants. For this purpose, four formulations were examined with regard to their physicochemical and in vitro drug release characteristics. Hot stage microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA),and X-ray diffraction showed cubic liquid crystalline and eutectic structures. The more suitable formulation consisting of 80-15-5%wt/wt monoolein-water-gentamicin sulfate progressively released the antibiotic for a period of 3 weeks without burst effect. Moreover, the content and the release profile of gentamicin sulfate were not significantly changed after storage at 2-6 degrees C for a period of 10 months.

Comptes Rendus Chimie, 2004

OPA is often used as an off-line derivatisation agent for fluorimetric detection in gentamicin an... more OPA is often used as an off-line derivatisation agent for fluorimetric detection in gentamicin analysis. As, in general, electrochemical detection is more sensitive than fluorimetric detection, the analysis of gentamicin as its OPA derivatives by high-performance liquid chromatography and electrochemical detection is proposed. The derivatisation procedure is that described by the European pharmacopoeia. The method allows not only the detection of all major gentamicin congeners C 1 , C 1A , C 2A and C 2 , but also of other minor unidentified components. A full validation of the method is presented and comparison is made with fluorimetric detection. A good linearity is found for the four congeners within the dynamic ranges 1-50 µg ml -1 for electrochemical detection and 4-80 µg ml -1 for fluorimetric detection. Both methods presented good accuracy and fidelity, although electrochemical detection is more sensitive than fluorimetric detection. The electrochemical detection method presented in this work appears to be a good alternative to the fluorimetric and pulsed electrochemical detection methods. To cite this article: I.T. Somé et al., C. R. Chimie 7 (2004). © 2004 Published by Elsevier SAS on behalf of Académie des sciences.

Communication et langages, 1976

Bioorganic & Medicinal Chemistry, 2010

A series of 33 novel divanillates and trivanillates were synthesized and found to possess promisi... more A series of 33 novel divanillates and trivanillates were synthesized and found to possess promising cytostatic rather than cytotoxic properties. Several compounds under study decreased by >50% the activity of Aurora A, B, and C, and WEE1 kinase activity at concentrations <10% of their IC(50) growth inhibitory ones, accounting, at least partly, for their cytostatic effects in cancer cells and to a lesser extent in normal cells. Compounds 6b and 13c represent interesting starting points for the development of cytostatic agents to combat cancers, which are naturally resistant to pro-apoptotic stimuli, including metastatic malignancies.