Synthesis and Biological Evaluation of CF3 Se-Substituted α-Amino Acid Derivatives

Abstract

Several CF₃ Se-substituted α-amino acid derivatives, such as (R)-2-amino-3-((trifluoromethyl)selanyl)propanoates (5 a/6 a), (S)-2-amino-4-((trifluoromethyl)selanyl)butanoates (5 b/6 b), (2R,3R)-2-amino-3-((trifluoromethyl)selanyl)butanoates (5 c/6 c), (R)-2-((S)-2-amino-3-phenylpropanamido)-3-((trifluoromethyl)selanyl)propanoates (11 a/12 a), and (R)-2-(2-aminoacetamido)-3-((trifluoromethyl)selanyl)propanoates (11 b/12 b), were readily synthesized from natural amino acids and [Me₄ N][SeCF₃ ]. The primary in vitro cytotoxicity assays revealed that compounds 6 a, 11 a and 12 a were more effective cell growth inhibitors than the other tested CF₃ Se-substituted derivatives towards MCF-7, HCT116, and SK-OV-3 cells, with their IC₅₀ values being less than 10 μM for MCF-7 and HCT116 cells. This study indicated the potentials of CF₃ Se moiety as a pharmaceutically relevant group in the design and synthesis of novel biologically active molecules.

Keywords: amino acid; biological activity; fluorine; synthesis; trifluoromethylseleno groups.