BIOACTIVITIES OF N-(4-HYDROXYPHENYL) RETINAMIDE AND RETINOYL BETA-GLUCURONIDE

N-(4-Hydroxyphenyl) retinamide (4HPR) and retinoyl beta-glucuronide (R AG) are two derivatives of all-trans retinoic acid (RA) that show prop erties both similar to as well as different from their parent compound , RA. Both retinoids possess the important property of showing much-re duced toxicity relative to RA while maintaining significant biological activity, 4HPR, a synthetic derivative, is active in the prevention a nd treatment of a variety of neoplasms in animals, and by inducing apo ptosis, shows growth inhibitory activity against many human tumor cell types in vitro. In humans, 4HPR reduces the incidence of new occurren ces of leukoplakia and is currently being tested as a preventive agent for breast cancer, RAG, a naturally occurring metabolite of RA, effec tively stimulates the growth of vitamin A-deficient animals, induces t he differentiation of epithelial cells in vivo and in vitro, and is ef fective in the topical treatment of acne in humans, Unlike RA, RAG is nontoxic when applied to the skin and is nonteratogenic when given ora lly to rats, Possible mechanisms of action of both compounds are discu ssed. These two derivatives of retinoids show interesting physiologic effects and potentially beneficial pharmacologic actions.