Team description

The CEMLS's group of the Chemical Science Institute of Rennes through the Bazureau and Carreaux's team focuses its research on 5 main axes:

i) the molecular design and synthetic development of low molecular weight five-membered heterocyclic platforms (FMHPs) as "privileged scaffolds" in medicinal chemistry for the synthesis of new series of specific protein kinase which can be transformed into potential drug candidates (especially for the CNS pathologies across an industrial-academic research program since 2010). For construction and molecular decoration (with appropriate building-blocks) of these various heterocyclic platforms, we privileged the use of microwave irradiation using solvent-free or solution phase reaction conditions (by JPB & FC);

ii) Boron chemistry and their applications in medicinal chemistry (by FC); His research interests are focused on the development of new methods for organic synthesis and natural product synthesis employing organoboron chemistry as the assembling tool. Discovery of protein kinase inhibitors constitutes also a great part of his research.

iii) the specific study of microwave irradiation in organic synthesis (solvent-free, solution phase or solid phase approach) for fundamental aspects of wave/material interactions and continuous flow microwave chemistry through successful EEC contracts of FP5, FP6, FP7 (by JPB & LP);

iv) the development of MRI and multimodal (MRI + TEP, MRI +CT, etc) contrasts agents. Actually, efforts are focused on the realization of a non toxic multimodal platform based on SPION (supermagnetic iron oxide nanoparticules) which can be easily associated to other types of imaging techniques, and also be functionalized to target cancer cells (by FG + SC);

v) the study of macromolecules structure and conformational changes involved by the interaction with biological targets or partners (protein-protein, protein-ligand, protein-membrane complexes). Those biological macromolecular complexes are investigated by solution NMR and spectroscopic techniques (circular dichroism, fluorimetry, UV-Vis spectrometry) (by SC).

Role in the network

1- The main goal of Bazureau's team in the IC Network (task 3) is focused on the synthetic development of new analogues of SKF 96365 (used as SOC inhibitor reference) to improve the selectivity for Orai and TRPC channels. Recent results issued from a structure-activity relation ship (SAR) showed that the choice of the platform inhibitor (substituted aromatic five-membered heterocycle with nitrogen atoms) has a strong impact on SOC inhibition. Actually, in collaboration with the Mignen's team at Brest, research funded by Ligue Contre le Cancer, we focused our efforts on appropriate molecular design for the length of side chain and its position on the aromatic heterocyclic platform in order to obtain a good selectivity and good inhibition for SOC channel. As possible, the organic synthesis for the construction of these new inhibitors will be realized under microwave according to the 12 rules of green chemistry (by JPB).

 

2- Carreaux's team: Development of metastasis causes the most serious clinical consequences of cancer being responsible for over 90% of cancer-related death. Our long-term goal is to shed light on non-voltage gated calcium (Ca2+)-channels as relevant and promising druggable targets to prevent tumor spreading. In this research plan we focus on melanoma tumor cells invasion and metastasis and will attempt to ascertain the relevance of the TRPV2 Ca2+ channel as bona fide therapeutic target to prevent dissemination of the tumors. For that we planned to synthesize new chemical TRPV2 modulators based on the Tranilast lead molecule and begin to screen for their anti-metastatic properties.

Involvement in tasks 3

 Discovery of SK3 and SOC modulators : SOCs modulators : pyrazoles triazoles and SKF-96355 analogs Task3.

 

 Synthesis of new chemical TRPV2 modulators based on the Tranilast lead molecule.

Valorizations/Collaborations

Publications / Patents

 

Synthetic development of new 3-(4-arylmethylamino)butyl-5-arylidene-rhodanines under microwave irradiation and their effects on tumor cell lines and against protein kinases. C.D. Dago, C.N. Ambeu, W.K. Coulibaly, Y-A. Bekro, J.A. Mamyrbekova-Bekro, A. Defontaine, B. Baratte, S. Bach, S. Ruchaud, R. Le Guével, M. Ravache, A. Corlu, J-P. Bazureau. Molecules 2015, 20, 12412-12435.

 

Prospective directed to the synthesis of unsymmetrical linked bis-5-arylidene rhodanine derivatives via "one-pot two steps" reactions under microwave irradiation with their antitumor activity. Coulibaly WK, Paquin L, Bénie A, Bekro YA, Le Guével R, Ravache M, Corlu A, Bazureau JP. Med. Chem. Res. 2015, 24, 1653-1661. doi: 10.1007/s00044-014-1186-7.

 

Microwave assisted prospective synthesis of new 5-arylidene rhodanine derivatives bearing an 3-[(4-(3-aminopropyl)piperazin-1-yl)propyl] chain. Ambeu N'ta C., Dago C-D., Coulibaly W-K, Mamyrbekova JA, Bekro Y-A, Anoubilé B, Bazureau J-P. Curr. Microwave Chem. 2015, 2, under press. doi: 10.2174/2213335602666150825215730.

 

New 5-ylidene rhodanine derivatives based on the Dispacamide A model. S. Guiheneuf, L. Paquin, F. Carreaux, E. Durieu, L. Meijer, J-P.Bazureau*. Molecular Diversity 2014, 18, 375-388.

 

Microwave Assisted Organic Synthesis (MAOS) of New Dispacamide A derivatives bearing a thiazolinone platform, biological assays on proteine kinases and cell effects. S. Guiheneuf, L. Paquin, F. Carreaux, E. Durieu, H. Bénédetti, R. Le Guével, A. Corlu, L. Meijer, J-P. Bazureau*. Curr. Microwave Chem. 2014, 1, 33-40.

 

Hemelaere, R.; Carreaux, F.; Carboni, B. Synthesis of Alkenyl Boronates from Allyl-Substituted Aromatics Using an Olefin Cross-Metathesis Protocol J. Org. Chem., 2013, 78, 6786.

 

An efficient approach to dispacamide A an its derivatives. S. Guiheneuf, L. Paquin, F. Carreaux, E. Durieu, L. Meijer, J-P. Bazureau*. Org. Biomol. Chem. 2012, 10, 978-987.

 

Microwaves in Heterocyclic Chemistry, Chapter 14, pp 673-766 in : Microwaves in Organic Chemistry, A.Loupy, A. de La Hoz, Eds., Third Edition, Wiley-VCH : Weinheim, Germany, 2012. J-P. Bazureau, L. Paquin, J-M. L'Helgoual'ch, D. Carrie, E. Limanton, S. Guiheneuf, G. Burgy, W-K. Coulibaly, S. Komaty. ISBN 978-3-527-33116-1

 

Synthesis of N,N'-bis(5-arylidene-4-oxo-3,5-dihydro-4H-imidazol-2-yl)diamines bearing various linkers and biological evaluation as potential inhibitors of kinases. W-K. Coulibaly, L. Paquin, A. Bénie, Y-A. Bekro, E. Durieu, L. Meijer, J-P.Bazureau*. Eur. J. Med. Chem. 2012, 58, 581-590.

 

Selectivity, co-crystal structures and neuroprotective properties of Leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid Leucettamine B. T. Tahtouh, O. Federov, M. Soundararajan, G. Burgy, E. Durieu, O. Lozach, C. Cochet, R-S. Schmid, D-C. Lo, F. Delhommel, A-E. Oberholzer, L-H. Pearl, F. Carreaux, J-P. Bazureau, S. Knapp, L. Meijer. J. Med. Chem. 2012, 55(21), 9312-9330.

 

Synthesis of new N,N'-bis(5-arylidene-4-oxo-4,5-dihydro-thiazolidine-2-yl)piperazine derivatives under microwave irradiation and preliminary biological evaluation. W-K. Coulibaly, L. Paquin, A. Bénie, Y-A. Bekro, E. Durieux, S. Rucheau, L. Meijer, R. Le Guével, A. Corlu, J-P. Bazureau*. Scient. Pharm. 2012, 80, 825-836.

 

An expeditious, environment-friendly, and microwave-assisted synthesis of new 5-isatinylidene rhodanine derivatives. A. Safer, M. Rahmouni, F. Carreaux, L. Paquin, O. Lozach, L. Meijer, J-P. Bazureau*. Chemical Papers 2011, 65(3), 332-337.

 

"Ultrasound and Microwave: Recent advances in organic chemistry", J.P. Bazureau, M. Draye, Eds, Transworld Research Signpost, Kerala, 2011. ISBN: 978-81-7895-532-2.

 

A practical approach to new (5Z) 2-alkylthio-5-arylidene-1-methyl-1,5-dihydro-4H-imidazol-4-one derivatives. K. Bourhala, L. Paquin, F. Carreaux, O. Lozach, L. Meijer, J-P. Bazureau*. Molecules 2011, 16, 7377-7390.

 

Design, synthesis and biological evaluation of leucettines, a class of potent CLK and DYRK kinases inhibitors derived from the marine sponge leucettamine B. Modulation of alternative RNA splicing. M. Debdab, F. Carreaux*, S. Renault, M. Soundararajan, O. Federov, O. Lozach, L. Babault, B. Baratte, Y. Ogawa, M. Hagiwara, A. Einsenreich, U. Rauch, S. Knapp, L. Meijer*, J-P. Bazureau*. J. Med. Chem. 2011, 54(12), 4172-4186.

 

Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid Leucettamine B as kinase inhibitors. M. Debdab, S. Renault, O. Lozach, L. Meijer, L. Paquin, F. Carreaux, J-P. Bazureau*. Eur. J. Med. Chem. 2010, 45, 805–810.

 

An efficient method for the preparation of new analogs of Leucettamine B under solvent-free microwave irradiation. M. Debdab, S. Renault, S. Eid, O. Lozach, L. Meijer, F. Carreaux*, J-P. Bazureau*. Heterocycles 2009, 78(5), 1191-1203.

Microwave mediated solventless synthesis of new derivatives of marine alkaloid Leucettamine B. J-R. Chérouvrier, F. Carreaux, J-P. Bazureau. Tet. Letters 2002, 43, 3581-3584.

 

A Practical Access to Novel 2-Amino-5-arylidene-thiazol-4-ones via Sulfur/nitrogen Displacement under Solvent-free Microwave Irradiations. K. Bourhala, A. Derdour, M. Rahmouni, F. Carreaux, J-P. Bazureau*. Tet. Letters 2007, 48, 5785-5789.

 

Parallel solution phase synthesis of 2-alkylthio-3,5-dihydro-4H-imidazol-4-one by one-pot three component domino reaction. S. Renault, S. Bertrand, F. Carreaux*, J-P. Bazureau*. J. Comb. Chem. 2007, 9, 935-942.

 

Brevets

Dérivés d'imidazolones, procédé de préparation et applications biologiques. J-P. Bazureau, F. Carreaux, S. Renault, L. Meijer, O. Lozach. Brevet FR 2 919 608 (A1) du 06 Février 2009. Fr. Demande 07/05632, dépôt du 01 Août 2007.

 

Imidazolone derivatives, preparation method thereof and biological use of same. J-P. Bazureau, F. Carreaux, S. Renault, L. Meijer, O. Lozach. Brevet WO 2009/05032 A2 du 23 Avril 2009. Demande PCT/FR 2008/001152 du 01/10/2008.

 

Dérivés de 5-arylidène rhodanine, procédé de préparation et applications biologiques. J-P. Bazureau, F. Carreaux, K. Bourhala, A. Safer, L. Paquin, L. Meijer, O. Lozach. Enveloppe Soleau, N°374 214 040 210 du 22 Février 2010.