N-(Retinoyl) amino acids. Synthesis and chemopreventive activity in vitro

• Published in: Journal of medicinal chemistry Vol. 31; no. 1; pp. 190 - 196
• Main Authors: Shealy, Y. Fulmer, Frye, Jerry L, Schiff, Leonard J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-01-1988
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Amino Acids - chemical synthesis; Amino Acids - pharmacology; Animals; Chemistry; Cricetinae; Exact sciences and technology; Indicators and Reagents; Metaplasia; Organ Culture Techniques; Organic chemistry; Preparations and properties; Retinoids - chemical synthesis; Retinoids - pharmacology; Structure-Activity Relationship; Terpenoids; Trachea - drug effects; Trachea - pathology; Stereoisomer; Toxicity; Rodentia; Organotypic culture; Cell differentiation; Vertebrata; Chemotherapy; Mammalia; Aminoester; Aminoacid; Acyl chloride; Epithelial cell; Protection; Trachea; Hamster
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00396a031

N-(all-trans-Retinoyl)amino acids were synthesized via all-trans-retinoyl chloride and an ester of the amino acid. The retinoyl derivatives of leucine, phenylalanine, alanine, tyrosine, and glutamic acid were prepared. The 13-cis-retinoyl derivatives of leucine, phenylalanine, alanine, and glycine were prepared similarly from 13-cis-retinoic acid. In assays of the retinoylamino acids for reversal of squamous metaplasia in hamster trachea organ cultures, these compounds were less active than retinoic acid, but the leucine, alanine, and phenylalanine derivatives were similar in activity to several retinamides that suppress bladder carcinogenesis in vivo. Two of the retinoylamino acids, as well as two simple retinamides, were shown to be moderately cytotoxic to murine leukemia and human epidermoid carcinoma cells in culture.