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A practical multi-step synthesis of ethyl N-functionalized \(\varvec{\upbeta }\)-amino benzimidazole acrylate derivatives as promising cytotoxic agents

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Abstract

A series of 16 new ethyl \(\upbeta \)-amino benzimidazole acrylate derivatives 12(a–p) with a (2E)-s-cis/trans conformation and bearing two points of diversity was designed and synthesized by using a multi-step strategy (reductive amination, deprotection in acidic media and transamination) in moderate to good yields from ethyl 3-dimethylamino-2-(1H-benzimidazol-2-yl)acrylate (5) and monosubstituted N-Boc diamines (7a,7b) as starting building blocks. Products 12 were evaluated for their in vitro cytotoxic potential against six selected human cell lines (Huh7-D12, Caco2, MDA-MB231, HCT116, PC3 and NCI-H727). Compounds 12a, 12e and 12l exhibited selective and micromolar antitumor activities against Huh7-D12 and Caco2 cell lines.

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Acknowledgements

One of us (C.N.A.) wishes to thank the "Elec-BTP" and the "Ministère de l’Enseignement Supérieur et de la Recherche Scientifique de Côte d’Ivoire" for grants. Financial support of this program carried out under the French National Cancer Institute “Cancéropôle Grand Ouest” by “Valorisation des produits de la mer en cancérologie” contract, is gratefully acknowledged. The authors are grateful to the assistance of the staff of the CRMPO analytical chemistry core facility for HRMS analysis (CRMPO platform, ScanMAT UMS 2001 CNRS, Université de Rennes 1, Bât. 11A, Campus de Beaulieu, Rennes, France).

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Authors and Affiliations

  1. Institut des Sciences Chimiques de Rennes (ISCR), UMR CNRS 6226, groupe COrInt, Université de Rennes 1 (UR1), Campus de Beaulieu, Bât. 10A, 263 Avenue du Général Leclerc, CS 74205, 35042, Rennes Cedex, France

    Christelle N’Ta Ambeu & Jean-Pierre Bazureau

  2. Laboratoire de Chimie Bio Organique et Substances Naturelles (LCBOSN), Université Nangui Abrogoua (UNA), 02 BP 801, Abidjan, Côte d’Ivoire

    Christelle N’Ta Ambeu & Janat Akhanovna Mamyrbekova

  3. Université de Rennes 1, ImPACcell Platform, SFR Biosit, Bât. 8, Campus Villejean, 2 Av. du Prof. Léon Bernard, CS 34317, 35043, Rennes Cedex, France

    Rémy Le Guével & Anne Corlu

  4. Université de Rennes 1, Inserm UMR 991, Hôpital Pontchaillou, 2 Rue Henri Le Guilloux, 35033, Rennes Cedex, France

    Anne Corlu

  5. S2Wave platform, ScanMAT UMS 2001 CNRS, Université de Rennes 1 (UR1), Campus de Beaulieu, Bât. 10A, 263 Avenue du Général Leclerc, CS 74205, 35042, Rennes Cedex, France

    Jean-Pierre Bazureau

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  1. Christelle N’Ta Ambeu
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  2. Rémy Le Guével
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  3. Anne Corlu
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  4. Janat Akhanovna Mamyrbekova
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Correspondence to Jean-Pierre Bazureau.

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Ambeu, C.N., Le Guével, R., Corlu, A. et al. A practical multi-step synthesis of ethyl N-functionalized \(\varvec{\upbeta }\)-amino benzimidazole acrylate derivatives as promising cytotoxic agents. Mol Divers 22, 685–708 (2018). https://doi.org/10.1007/s11030-018-9824-5

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