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

Abstract

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.

Retinoic Acid Conjugates as Potential Antitumor Agents: Synthesis and Biological Activity of Conjugates with Ara-A, Ara-C, 3(2H)-Furanone, and Aniline Mustard Moieties

“…The low activity of the mustard 12 and the diamide 14 indicates that these molecules may act, as intact entities, as retinoic acid analogues rather than as carriers for the two moieties, this being partially in contrast with the reported prominent retinoidal activity of simple as well as complex retinamides. 31,32 Experimental Section Chemistry. Material and Methods.…”

Effect of conjugates of all-trans-retinoic acid and shorter polyene chain analogues with amino acids on prostate cancer cell growth

“…The amino acids used were Gly, Ala, Leu, Phe, Tyr, and Glu. All of the thus examined conjugates were less active than ATRA [11]. In that bioassay, most active amino acid was Leu, incorporating a lipophilic side chain, and least active Glu, with a polar side chain.…”

“…The conjugates (3)(4)(5)(6)(7)(8)(9)(10)(11) of amino acids with ATRA and analogues with shorter polyene chain, which were synthesized in the context of the present work, are depicted in Figs. 1 and 2.…”

Cancer Chemopreventive Retinoids: Validation and Analysis of <i>in Vivo</i> and <i>in Vitro</i> Bioassay Results

“…(Table 3). Figure 5 shows the general structural formula of retinoyl amino acid compounds [26], Table 3. Effect of many different 4-oxoretinoic acid derivatives and some bifunctional compounds on the suppression of tumorigeneis nesis in the mouse skin papilloma bioassay.…”