Retinoid, synthetic

Vitamin A (retinol) and its naturally occurring and synthetic derivatives, collectively referred to as retinoids (chemical structure), exert a wide variety of profound effects in apoptosis, embryogenesis, reproduction, vision, and regulation of inflammation, growth, and differentiation of normal and neoplastic cells in vertebrates. 

Synthetic Retinoid Receptor Selective Agonists/ Antagonists... 

These arotinoids, which were first introduced for the treatment of skin diseases, may also have potential as anticancer diugs. For example, the synthetic retinoid 6-[3-(l-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) has been shown to induce apoptosis in a variety of cancer cells including lung cancer cells in vitro, and studies concerning the use of this agent in vivo would be desirable. 

Kagechika H (2002) Novel synthetic retinoids and separation of the pleiotrophc retinoidal activities. Curr Med Chem 9(5) 591-608... 

Tazarotene is a synthetic retinoid that mediates cell differentiation and proliferation [19]. Tazarotene, a pro-drug of tazarotenic acid,has recently been proven effective as a treatment for photodamaged skin [11]. 

Araki, H., Y. Shidoji, Y. Yamada, H. Moriwaki, and Y. Muto. 1995. Retinoid agonist activities of synthetic geranyl geranoic acid derivatives. Biochem Biophys Res Commun 209(l) 66-72. 

Pasquali, D, V Rossi, G Bellastella, A Ballastella, and AA Sinisi. 2006. Natural and synthetic retinoids in prostate cancer. Curr Pharm Des 12 1923-1929. 

Tazarotene (Tazorac) is a synthetic acetylenic retinoid that is converted to its active form, tazarotenic acid, after topical application. 

Tazarotene (Tazorac) is a synthetic retinoid that is hydrolyzed to its active metabolite, tazarotenic acid, which modulates keratinocyte proliferation and differentiation. It is available as a 0.05% or 0.1% gel and cream and is applied once daily (usually in the evening) for mild to moderate plaque psoriasis. Adverse effects are dose- and frequency related and include mild to moderate pruritus, burning, stinging, and erythema. Application of the gel to eczematous skin or to more than 20% of body surface area is not recommended because this may lead to extensive systemic absorption. Tazarotene is often used with topical corticosteroids to decrease local adverse effects and increase efficacy. 

N. Krause, in Chemistry and Biology of Synthetic Retinoids, M. I. Dawson,... 

Likewise, retinoic acid (11) and its derivatives [40,41], as well as synthetic aromatic retinoids (arotinoids) [42,43], inhibited A23187-stimulated release... 

This class includes both vitamin A and the provitamin A carotenoids. All the compounds related to all-trani-retinol (Figure 19.11) are known as vitamin A. These compounds, together with their metabolites and synthetic derivatives, exhibiting the same properties are called retinoids. Vitamin A is found in animal products as retinyl esters (mainly palmitate). 

Isotretinoin, or 13-cis-retinoic acid, and etretinate are available for oral administration. Isotretinoin is a synthetic retinoid that is used for sever cystic acne, recalcitrant to standard therapies. Its mechanism of action is not well understood but involves the inhibition of sebaceous gland size and function. 

Retinoids are a family of naturally occurring and synthetic analogues of vitamin A. The skin of subjects deficient in vitamin A becomes hyperplastic and keratotic (phrynoderma, or toad skin). While natural vitamin A is occasionally employed therapeutically, synthetic retinoids are more effective and represent a major advance in dermatological pharmacotherapy. Retinoids have myriad effects on cellular differentiation and proliferation it is likely that nuclear retinoic acid receptors mediate these effects by activating gene expression in a manner analogous to receptors for steroid hormones and thyroid hormones. Despite a common mechanism of action, however, retinoids vary widely in their physiological effects. 

Isotretinoin is a synthetic retinoid which acts by inhibiting sebaceous gland size and function. 

Isotretinoin (Accutane) is a synthetic retinoid currently restricted to the oral treatment of severe cystic acne that is recalcitrant to standard therapies. The precise mechanism of action of isotretinoin in cystic acne is not known, although it appears to act by inhibiting sebaceous gland size and function. The drug is well absorbed, extensively bound to plasma albumin, and has an elimination half-life of 10-20 hours. 

Vitamin A is often used as a collective term for several related bio logically active molecules (Figure 28.18). The term retinoids includes both natural and synthetic forms of vitamin A that may or may not show vitamin A activity. 

Although the term vitamin A has been used to denote specific chemical compounds, such as retinol or its esters, this term now is used more as a generic descriptor for compounds that exhibit the biological properties of retinol. Retinoid refers to the chemical entity retinol or other closely related naturally occurring derivatives. Retinoids also include structurally related synthetic analogues, which need not have retinol-like (vitamin A) activity. The structural formulas for the vitamin A family of retinoids are shown in Figure 66.3. Retinol (vitamin Aj), a primary alcohol, is present in esterihed form in the tissues of animals and saltwater fish, mainly in the liver. A closely related compound, 3-dehydroretinol (vitamin A2), is obtained from the tissues of freshwater fish and usually occurs mixed with retinol. 

Modulation of Mutagenesis by 3-carotene and 13-cis-Retinoic Acid. The provitamin 3-carotene, and a synthetic derivative of vitamin A, 13-cis-retinoic acid, were examined with respect to their capacity to modulate 2-fluorenamine-induced mutagenicity in Salmonella. These studies were carried out since dietary and serum levels of 3-carotene vary widely among humans. Also, there is considerable interest in the anti-tumor activity of 13-cis-retinoic acid and other synthetic retinoids. 

In no instance did the synthetic retinoid possess as great an inhibitory capacity as do retinol or retinyl acetate. In addition, the provitamin g-carotene had no effect on mutagenicity of 2-fluorenamine in Salmonella regardless of the carcinogen activation system (Tables III and IV). Thus, 3-carotene would apparently require enzymatic cleavage to vitamin A in order to have an effect in this ijri vitro bioassay and exerts no role by itself in modulating the metabolism of chemical carcinogens in the model system. 

Similar effects were observed with the synthetic retinoid 13-cis-retinoic acid, while 3-carotene was without effect in modulating the mutagenicity of aromatic amines in Salmonella. 

---