Daniel Dauzonne
Curie Institute
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Featured researches published by Daniel Dauzonne.
Medicinal Research Reviews | 2006
Brigitte Bauvois; Daniel Dauzonne
Aminopeptidase N (APN)/CD13 (EC 3.4.11.2) is a transmembrane protease present in a wide variety of human tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). APN/CD13 expression is dysregulated in inflammatory diseases and in cancers (solid and hematologic tumors). APN/CD13 serves as a receptor for coronaviruses. Natural and synthetic inhibitors of APN activity have been characterized. These inhibitors have revealed that APN is able to modulate bioactive peptide responses (pain management, vasopressin release) and to influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis). Therefore, inhibition of APN/CD13 may lead to the development of anti‐cancer and anti‐inflammatory drugs. This review provides an update on the biological and pharmacological profiles of known natural and synthetic APN inhibitors. Current status on their potential use as therapeutic agents is discussed with regard to toxicity and specificity.
PLOS Pathogens | 2013
Marianne Lucas-Hourani; Daniel Dauzonne; Pierre Jorda; Gaëlle Cousin; Alexandru Lupan; Olivier Helynck; Grégory Caignard; Geneviève Janvier; Gwénaëlle André-Leroux; Samira Khiar; Nicolas Escriou; Philippe Desprès; Yves Jacob; Hélène Munier-Lehmann; Frédéric Tangy; Pierre-Olivier Vidalain
Searching for stimulators of the innate antiviral response is an appealing approach to develop novel therapeutics against viral infections. Here, we established a cell-based reporter assay to identify compounds stimulating expression of interferon-inducible antiviral genes. DD264 was selected out of 41,353 compounds for both its immuno-stimulatory and antiviral properties. While searching for its mode of action, we identified DD264 as an inhibitor of pyrimidine biosynthesis pathway. This metabolic pathway was recently identified as a prime target of broad-spectrum antiviral molecules, but our data unraveled a yet unsuspected link with innate immunity. Indeed, we showed that DD264 or brequinar, a well-known inhibitor of pyrimidine biosynthesis pathway, both enhanced the expression of antiviral genes in human cells. Furthermore, antiviral activity of DD264 or brequinar was found strictly dependent on cellular gene transcription, nuclear export machinery, and required IRF1 transcription factor. In conclusion, the antiviral property of pyrimidine biosynthesis inhibitors is not a direct consequence of pyrimidine deprivation on the virus machinery, but rather involves the induction of cellular immune response.
European Journal of Medicinal Chemistry | 1997
Daniel Dauzonne; B Folléas; L Martinez; Gg Chabot
Summary To further understand the molecular requirements for the antiproliferative activity of flavonoids, a series of 3-amino-flavones and some of their derivatives were prepared and evaluated using L1210 murine leukemia. Our novel five-step synthetic approach required easily available substituted aromatic aldehydes as starting materials and proved more convenient and more general than previously reported methods. Our results in the 3-aminoflavones series indicated that the 4′-methoxy group is important for cytotoxic activity. Moreover, for the flavone-8-acetic analogs, a marked increase in potency was observed with the addition of a 3-amino or a 3-nitro group. Methoxy groups on the 6 and 7 positions of flavonoids (as in cirsiliol) also appear to be important for antiproliferative activity. These results are essential for the further understanding of the critical molecular requirements that lead to antiproliferative properties in the flavonoid series.
ChemBioChem | 2011
Alexandre Ceccaldi; Arumugam Rajavelu; Christine Champion; Christine Rampon; Renata Z. Jurkowska; Gytis Jankevicius; Catherine Senamaud-Beaufort; Loïc Ponger; Nathalie Gagey; Hana Dali Ali; Jörg Tost; Sophie Vriz; Sindu Ros; Daniel Dauzonne; Albert Jeltsch; Dominique Guianvarc'h; Paola B. Arimondo
DNA methylation is involved in the regulation of gene expression and plays an important role in normal developmental processes and diseases, such as cancer. DNA methyltransferases are the enzymes responsible for DNA methylation on the position 5 of cytidine in a CpG context. In order to identify and characterize novel inhibitors of these enzymes, we developed a fluorescence‐based throughput screening by using a short DNA duplex immobilized on 96‐well plates. We have screened 114 flavones and flavanones for the inhibition of the murine catalytic Dnmt3a/3L complex and found 36 hits with IC50 values in the lower micromolar and high nanomolar ranges. The assay, together with inhibition tests on two other methyltransferases, structure–activity relationships and docking studies, gave insights on the mechanism of inhibition. Finally, two derivatives effected zebrafish embryo development, and induced a global demethylation of the genome, at doses lower than the control drug, 5‐azacytidine.
European Journal of Medicinal Chemistry | 2012
Núria Mur Blanch; Guy G. Chabot; Lionel Quentin; Daniel Scherman; Stéphane Bourg; Daniel Dauzonne
To find new and better antivascular agents for cancer therapy, a series of combretastatin A4 (CA4) analogs were prepared from 1,3-diaryl-2-nitroprop-1-enes (6-12) obtained in a two-step synthesis from appropriate arylaldehydes and 2-aryl-1-nitroethanes (4 or 5). Treatment of these 1,3-diaryl-2-nitroprop-1-enes 6-12 by sodium azide in DMSO yielded the targeted compounds. The synthesized 1,2,3-triazoles disubstituted in 4- and 5-positions by one benzyl group and one aryl nucleus have also been tested for biological activities involved in antivascular action. It was found that several new compounds exhibited interesting biological activities in the nanomolar or low micromolar range, in terms of rounding up of endothelial cells, inhibition of tubulin polymerization, and cytotoxicity on B16 melanoma cancer cells. In silico docking studies of 11 and 19 within the active site of tubulin were also carried out in order to rationalize the inhibitory properties of these compounds and further understand their inhibition mechanism. In vivo evaluation of compounds 11 and 19 in mice bearing colon 26 carcinoma indicated modest anticancer activity.
Nucleic Acids Research | 2006
Maria Duca; Dominique Guianvarc'h; Kahina Oussedik; Ludovic Halby; Anna Garbesi; Daniel Dauzonne; Claude Monneret; Neil Osheroff; Carine Giovannangeli; Paola B. Arimondo
Human topoisomerase II (topo II) is the cellular target for a number of widely used antitumor agents, such as etoposide (VP16). These agents ‘poison’ the enzyme and induce it to generate DNA breaks that are lethal to the cell. Topo II-targeted drugs show a limited sequence preference, triggering double-stranded breaks throughout the genome. Circumstantial evidence strongly suggests that some of these breaks induce chromosomal translocations that lead to specific types of leukaemia (called treatment-related or secondary leukaemia). Therefore, efforts are ongoing to decrease these secondary effects. An interesting option is to increase the sequence-specificity of topo II-targeted drugs by attaching them to triplex-forming oligonucleotides (TFO) that bind to DNA in a highly sequence-specific manner. Here five derivatives of VP16 were attached to TFOs. The active topo II poisons, once linked, induced cleavage 13–14 bp from the triplex end where the drug was attached. The use of triple-helical DNA structures offers an efficient strategy for targeting topo II-mediated cleavage to DNA specific sequences. Finally, drug–TFO conjugates are useful tools to investigate the mechanistic details of topo II poisoning.
European Journal of Medicinal Chemistry | 1995
Daniel Dauzonne; Jm Gillardin; F Lepage; R Pointet; S. Risse; G Lamotte; Pierre Demerseman
Summary A series of novel benzofuranylacryloylpiperazines, which are structurally related to both cinnamamide derivatives and befuraline, have been prepared as their hydrochlorides. Their anticonvulsant and antidepressant activities against seizures induced by electroshock and against tetrabenazine-induced palpebral ptosis have been evaluated in mice. Some of them revealed interesting potencies since, although they are less active than the reference drugs, they exhibited a higher protective index.
Tetrahedron | 1990
Daniel Dauzonne; Hubert Josien; Pierre Demerseman
Abstract we describe a convenient and general method for the preparation of 2,3-dihydro-2-nitro-3-phenyl-4 H -furo[3,2-c] [1]benzopyran-4-ones from 4-hydroxy-coumarin and (2-chloro-2-nitroethenyl)benzenes in the presence of potassium fluoride. Using the same starting materials and by replacing potassium fluoride with triethylamine the hitherto unknown 3-phenyl-4 H -furo[3,2-c] [1]benzopyran-4-ones are obtained in a one-pot procedure.
Tetrahedron Letters | 1995
Daniel Dauzonne; Laetitia Martinez
The synthesis of the so far unknown 3-amino-4-oxo-2-phenyl-4H-1-benzopyran-8-acetic acid (3-aminoflavone-8-acetic acid) starting from 2-hydroxy-3-(prop-2-ene)benzaldehyde and (Z)-(2-chloro-2-nitroethenyl)benzene is described.
Biochemistry | 2011
Steven L. Pitts; Michael J. Jablonksy; Maria Duca; Daniel Dauzonne; Claude Monneret; Paola B. Arimondo; Clemens Anklin; David E. Graves; Neil Osheroff
Etoposide is a widely prescribed anticancer drug that stabilizes covalent topoisomerase II-cleaved DNA complexes. The drug contains a polycyclic ring system (rings A-D), a glycosidic moiety at C4, and a pendant ring (E-ring) at C1. Interactions between human topoisomerase IIα and etoposide in the binary enzyme--drug complex appear to be mediated by substituents on the A-, B-, and E-rings of etoposide. These protein--drug contacts in the binary complex have predictive value for the actions of etoposide within the ternary topoisomerase IIα--drug--DNA complex. Although the D-ring of etoposide does not appear to contact topoisomerase IIα in the binary complex, etoposide derivatives with modified D-rings display reduced cytotoxicity against murine leukemia cells [Meresse, P., et al. (2003) Bioorg. Med. Chem. Lett. 13, 4107]. This finding suggests that alterations in the D-ring may affect etoposide activity toward topoisomerase IIα in the ternary enzyme--drug--DNA complex. Therefore, to address the potential contributions of the D-ring to the activity of etoposide, we characterized drug derivatives in which the C13 carbonyl was moved to the C11 position (retroetoposide and retroDEPT) or the D-ring was opened (D-ring diol). All of the D-ring alterations decreased the ability of etoposide to enhance DNA cleavage mediated by human topoisomerase IIα in vitro and in cultured cells. They also weakened etoposide binding in the ternary enzyme--drug--DNA complex and altered sites of enzyme-mediated DNA cleavage. On the basis of these findings, we propose that the D-ring of etoposide has important interactions with DNA in the ternary topoisomerase II cleavage complex.