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1.
Vanessa Desplat Ambre Geneste Marc-Antoine Begorre Solene Belisle Fabre Stephane Brajot Stephane Massip 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):648-658
Akt kinases are attractive targets for small molecule drug discovery because of their key role in tumor cell survival/proliferation and their overexpression/activation in many human cancers. Recent efforts in the development and biological evaluation of small molecule inhibitors of Akt have led to the identification of novel Akt kinase inhibitors, based on a quinoxaline or pyrazinone scaffold. A series of new substituted pyrrolo[1,2-a]quinoxaline derivatives, structural analogues of these active quinoxaline or pyrazinone pharmacophores, was synthesized from various substituted 2-nitroanilines or 1,2-phenylenediamine via multistep heterocyclization process. These new compounds were tested for their in vitro ability to inhibit the proliferation of the human leukemic cell lines K562, U937 and HL60, and the breast cancer cell line MCF7. Three of these human cell lines (K562, U937 and MCF7) exhibited an active phosphorylated Akt form. The most promising active pyrroloquinoxalines were found to be 1a that inhibited K562 cell line proliferation with an IC50 of 4.5 μM, and 1h that inhibited U937 and MCF7 cell lines with IC50 of 5 and 8 μM, respectively. These two candidates exhibited more potent activities than the reference inhibitor A6730. 相似文献
2.
Thomas Landes Ingrid Leroy Ambre Bertholet Alan Diot Farnoosh Khosrobakhsh Marlène Daloyau Noélie Davezac Marie-Christine Miquel Delphine Courilleau Emmanuelle Guillou Aurélien Olichon Guy Lenaers Laetitia Arnauné-Pelloquin Laurent J. Emorine Pascale Belenguer 《Seminars in cell & developmental biology》2010,21(6):593-598
Mitochondrial morphology varies according to cell type and cellular context from an interconnected filamentous network to isolated dots. This morphological plasticity depends on mitochondrial dynamics, a balance between antagonistic forces of fission and fusion. DRP1 and FIS1 control mitochondrial outer membrane fission and Mitofusins its fusion. This review focuses on OPA1, one of the few known actors of inner membrane dynamics, whose mutations provoke an optic neuropathy. Since its first identification in 2000 the characterization of the functions of OPA1 has made rapid progress thus providing numerous clues to unravel the pathogenetic mechanisms of ADOA-1. 相似文献
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Vijay M. Khedkar Premlata K. Ambre Jitender Verma Mushtaque S. Shaikh Raghuvir R. S. Pissurlenkar Evans C. Coutinho 《Journal of molecular modeling》2010,16(7):1251-1268
HIV-1 protease is an obligatory enzyme in the replication process of the HIV virus. The abundance of structural information
on HIV-1PR has made the enzyme an attractive target for computer-aided drug design strategies. The daunting ability of the
virus to rapidly generate resistant mutants suggests that there is an ongoing need for new HIV-1PR inhibitors with better
efficacy profiles and reduced toxicity. In the present investigation, molecular modeling studies were performed on a series
of 54 cyclic urea analogs with symmetric P2/P2′ substituents. The binding modes of these inhibitors were determined by docking.
The docking results also provided a reliable conformational superimposition scheme for the 3D-QSAR studies. To gain insight
into the steric, electrostatic, hydrophobic and hydrogen-bonding properties of these molecules and their influence on the
inhibitory activity, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)
were performed. Two different alignment schemes viz. receptor-based and atom-fit alignment, were used in this study to build the QSAR models. The derived 3D-QSAR models were found to be robust with statistically
significant r
2
and r
2
pred
values and have led to the identification of regions important for steric, hydrophobic and electronic interactions. The predictive
ability of the models was assessed on a set of molecules that were not included in the training set. Superimposition of the
3D-contour maps generated from these models onto the active site of enzyme provided additional insight into the structural
requirements of these inhibitors. The CoMFA and CoMSIA models were used to design some new inhibitors with improved binding
affinity. Pharmacokinetic and toxicity predictions were also carried out for these molecules to gauge their ADME and safety
profile. The computational results may open up new avenues for synthesis of potent HIV-1 protease inhibitors. 相似文献
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A recently published study has revealed the genome-wide dynamics of DNA methylation and hydroxymethylation patterns at single-base resolution in the human and mouse developing brain. 相似文献
6.
Mauricio Lopez-Obando Ambre Guillory Franois-Didier Boyer David Cornu Beate Hoffmann Philippe Le Bris Jean-Bernard Pouvreau Philippe Delavault Catherine Rameau Alexandre de Saint Germain Sandrine Bonhomme 《The Plant cell》2021,33(11):3487
In angiosperms, the α/β hydrolase DWARF14 (D14), along with the F-box protein MORE AXILLARY GROWTH2 (MAX2), perceives strigolactones (SL) to regulate developmental processes. The key SL biosynthetic enzyme CAROTENOID CLEAVAGE DIOXYGENASE8 (CCD8) is present in the moss Physcomitrium patens, and PpCCD8-derived compounds regulate moss extension. The PpMAX2 homolog is not involved in the SL response, but 13 PpKAI2LIKE (PpKAI2L) genes homologous to the D14 ancestral paralog KARRIKIN INSENSITIVE2 (KAI2) encode candidate SL receptors. In Arabidopsis thaliana, AtKAI2 perceives karrikins and the elusive endogenous KAI2-Ligand (KL). Here, germination assays of the parasitic plant Phelipanche ramosa suggested that PpCCD8-derived compounds are likely noncanonical SLs. (+)-GR24 SL analog is a good mimic for PpCCD8-derived compounds in P. patens, while the effects of its enantiomer (−)-GR24, a KL mimic in angiosperms, are minimal. Interaction and binding assays of seven PpKAI2L proteins pointed to the stereoselectivity toward (−)-GR24 for a single clade of PpKAI2L (eu-KAI2). Enzyme assays highlighted the peculiar behavior of PpKAI2L-H. Phenotypic characterization of Ppkai2l mutants showed that eu-KAI2 genes are not involved in the perception of PpCCD8-derived compounds but act in a PpMAX2-dependent pathway. In contrast, mutations in PpKAI2L-G, and -J genes abolished the response to the (+)-GR24 enantiomer, suggesting that PpKAI2L-G, and -J proteins are receptors for moss SLs. The study of moss PpKAI2L receptors for strigolactones and related compounds highlights MORE AXILLARY GROWTH2-dependent and -independent pathways for the perception of these compounds. 相似文献
7.
Geographically distinct patterns of reproductive isolation and hybridization in two sympatric species of the Jaera albifrons complex (marine isopods)
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8.
Diana Mendes Freire Claude Gutierrez Acely Garza-Garcia Anna D. Grabowska Ambre J. Sala Kanchiyaphat Ariyachaokun Terezie Panikova Katherine S.H. Beckham André Colom Vivian Pogenberg Michele Cianci Anne Tuukkanen Yves-Marie Boudehen Antonio Peixoto Laure Botella Dmitri I. Svergun Dirk Schnappinger Thomas R. Schneider Olivier Neyrolles 《Molecular cell》2019,73(6):1282-1291.e8
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Plant Molecular Biology - Most known phytohormones regulate moss development. We present a comprehensive view of the synthesis and signaling pathways for the most investigated of these compounds in... 相似文献
10.
Ambre Ribardire Elsa Pabion Jrme Coudret Claire Daguin‐Thibaut Cline Houbin Stphane Loisel Sbastien Henry Thomas Broquet 《Journal of evolutionary biology》2021,34(1):33-48
Sexual barriers associated with mate choice are often found to be associated with some level of ecological isolation between species. The independence and relative strength of sexual isolation are thus difficult to assess. Here, we take advantage of a pair of marine isopod species (Jaera albifrons and J. praehirsuta) that show sexual isolation and coexist in populations where they share the same microhabitat or not (i.e. without or with ecological isolation). We estimated the strength of sexual isolation between J. albifrons and J. praehirsuta using no‐choice trials and a multiple‐choice experimental population. We found that sexual isolation is strong in both the presence and the absence of ecological isolation, but that it is asymmetric and fails to prevent interspecific gene flow entirely. First‐generation intrinsic post‐zygotic barriers were low, and there was no sexual isolation within J. praehirsuta across habitats. The J. albifrons/J. praehirsuta species pair thus provides an example where the role of sexual isolation as a barrier to gene flow (a) does not depend upon current ecological isolation, (b) seems to have evolved independently of local ecological conditions, but (c) is insufficient to complete speciation entirely on its own. 相似文献