Retinoids structure-activity relationships

Several other assays of retinoid activity exist [83] and include evaluations of the ability of a retinoid to inhibit the exponential growth of S91 murine melanoma cells or to induce terminal differentiation of the fully neoplastic F9 teratocarcinoma cells. These and other assays of retinoid activity have been useful but the TOC, ODC, and HL-60 assays have been used most comprehensively in establishing retinoid structure-activity relationships, which are discussed below. 

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. 

Chen LC, Berberian I, Koch B, et al. 1992. Polychlorinated and polybrominated biphenyl congeners and retinoid levels in rat tissues Structure-activity relationships. Toxicol Appl Pharmacol 114 47-55. 

C. M., Goldman, M.E. and Heyman, R.A. (1994) Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. Journal of Medicinal Chemistry, 37, 2930-2941. 

Douguet D, Thoreau E, Grassy G. Quantitative structure-activity relationship studies of RAR a, b, g retinoid agonists. Quant Struct-Act Relat 1999 18 107—123. 

Kagechika H, Kawachi E, Hashimoto Y, et al. Retinobenzoic acids. I. Structure-activity relationships of aromatic amides with retinoidal activity. Journal of Medicinal Chemistry 32(12), 2583, 1989. 

Structure-activity relationships of several retinoids were investigated. The most active retinoid is listed here. Exponential growth rate was not affected by retinoids, but saturation density was decreased. 

Beard RL, Chandraratna RAS, Colon DF, Gillett SJ, Henry E, Marler DK, Song T, Denys L, Garst ME, Arefieg T et al (1995) Synthesis and structure-activity relationships of stilbene retinoid analogs substituted with heteroaromatic carboxylic acids. J Med Chem 38 2820-2829... 

Beard RL, Colon DF, Song TK, Davies PJA, Kochhar DM, Chandraratna RAS (1996) Synthesis and structure-activity relationships of retinoid X receptor selective diaryl sulfide analogs of retinoic acid. J Med Chem 39 3556-3563... 

Adams J (1993) Structure-activity and dose-response relationships in the neural and behavioral teratogenesis of retinoids. Neurotoxicol Teratol, 15(3) 193-202. 

The relationship between retinoid structure and retinoid activity has been extensively studied. Because of the large number of geometric isomers and conformers possible with the conjugated retinoid skeleton, a multitude of isomeric and/or conformationally-locked retinoids have been synthesized to determine the shape and size of the binding site of the putative retinoid receptor. Several methods exist for evaluation of retinoid activity. A fair... 

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. 

Horton, C. and Maden, M. (1995) Endogenous distribution of retinoids during normal development and teratogenesis in the mouse embryo. Dev. Dynam. 202,312-323. Spom, M. B., Dunlop, V. M Newton, D. L., and Henderson, N. R. (1976) Relationships between structure and activity of retinoids. Nature 263,110-113. 

Biological Methods for Analysis and Assay of Retinoids— Relationships between Structure and Activity... 

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