A practical multi-step synthesis of ethyl N-functionalized β-amino benzimidazole acrylate derivatives as promising cytotoxic agents

Christelle N'Ta Ambeu (1, 2) , Rémy Le Guével (3) , Anne Corlu (3, 4) , Janat Akhanovna Mamyrbekova (2) , Jean-Pierre Bazureau (1, 5, 6)

1 ISCR - Institut des Sciences Chimiques de Rennes
2 UNA - Université Nangui Abrogoua
3 ImPACcell - Plate-forme ImPACcell
4 NuMeCan - Nutrition, Métabolismes et Cancer
5 Biosit : Biologie - Santé - Innovation Technologique - Structure Fédérative de Recherche en Biologie et Santé de Rennes
6 ScanMAT - Synthèse Caractérisation Analyse de la Matière

A series of 16 new ethyl [Formula: see text]-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.

Keywords: transamination; cytotoxicity; reductive amination; microwave; benzimidazole

Domains: Chemical Sciences; Medicinal Chemistry; Chemical Sciences; Organic chemistry

Christelle N'Ta Ambeu, Rémy Le Guével, Anne Corlu, Janat Akhanovna Mamyrbekova, Jean-Pierre Bazureau. A practical multi-step synthesis of ethyl N-functionalized β-amino benzimidazole acrylate derivatives as promising cytotoxic agents. Molecular Diversity, 2018, 22 (3), pp.685-708. ⟨10.1007/s11030-018-9824-5⟩. ⟨hal-01808102⟩