Retinoids structure-toxicity relationships

Both cell cultures and animal studies have shown that many of the naturally occurring mono-, sesqui-, di-, sester-, and meroterpenoids as well as retinoids possess potentially chemopreventive activities. Terpenoids are minor but ubiquitous components of our diet, and have the advantage of being non-toxic or relatively non-toxic to humans. More mechanistic-oriented basic research is needed to elucidate the mechanisms of action. Studies of derivatives of these naturally occurring terpenoids are also necessary to elucidate the structure-activity relationship and to guide the development of novel chemopreventive agents. 

The sophisticated chemical techniques described in Chapter 2 have led to the synthesis of more than a thousand new retinoids in laboratories throughout the world during the past 10 years. To obtain an adequate evaluation of the biological activity and toxicity of these new retinoids, a series of tests that measure activity both in vitro and in vivo is required. No single test alone is adequate. Organ and cell culture methods are extremely sensitive and have been particularly useful for studying structure-function relationships, whereas in vivo methods offer the possibility of predicting clinical utility. However, all methods have some liabilities, which include problems such as technical difficulty, limitations in the types of retinoids that can be assayed, or failure to detect useful retinoids. 

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