Analogues, vitamin, effect

Toxopyrimidine (pyramin lOlO) may be obtained from thiamine (vitamin Bi 1011) by acidic hydrolysis or by treatment with the thiaminase of Bacillus aneurinolyticus. Toxopyrimidine produces convulsions and death in rodents as do analogues, e.g. 2,4-dimethylpyrimidin-5-ylmethanol (1012) (65JMC750), but the effect is minimized or even... 

Phoenix, J., Edwards, R,H.T. and Jackson, M.J. (1991). The effect of vitamin E analogues and long hydrocarbon chain compounds on calcium-induced muscle damage a novel role for a-tocopherol. Biochim. Biophys. Acta. 1097, 212-218. 

Kaneko et al. (1993) have described a group of lipophilic ascorbic-acid analogues that have been studied in cultured human umbilical vein endothelial cells that were first incubated with test drug and then exposed to lipid hydroperoxides. Although ascorbate itself did not protect the endothelial cells, derivatives like CV3611 protected. Pretreatment was necessary. CV3611 was synergistic with vitamin E. The authors concluded that these lipophilic antioxidants incorporate into endothelial cell membranes where they are effective inhibitors of lipid peroxidation. In contrast, lipophobic antioxidants were not effective in their hands (Kaneko et al., 1993). 

The precise mechanism of dimethylhydrazine toxicity is uncertain. In addition to the contact irritant effects, the acute effects of dimethylhydrazine exposure may involve the central nervous system as exemplified by tremors and convulsions (Shaffer and Wands 1973) and behavioral changes at sublethal doses (Streman et al. 1969). Back and Thomas (1963) noted that the deaths probably involve respiratory arrest and cardiovascular collapse. The central nervous system as a target is consistent with the delayed latency in response reported for dimethylhydrazine (Back and Thomas 1963). There is some evidence that 1,1-dimethylhydrazine may act as an inhibitor of glutamic acid decarboxylase, thereby adversely affecting the aminobutyric acid shunt, and could explain the latency of central-nervous-system effects (Back and Thomas 1963). Furthermore, vitamin B6 analogues that act as coenzymes in the aminobutyric acid shunt have been shown to be effective antagonists to 1,1-dimethylhydrazine toxicity (reviewed in Back and Thomas 1963). 

The bisphosphonates are all analogues of pyrophosphate. They inhibit osteoclast resorption of bone and they are able to inhibit the formation and dissolution of hydroxyapatite crystals, however their exact mechanism is not well understood. Other effects which have relevance for bone homeostasis include inhibition of the activities of PTH, prostaglandins and 1,25-dihydroxy vitamin D. Bisphosphonates bind to bone with high affinity. They have therefore a duration of action that continues long after their use has been stopped. 

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. 

Biochemical studies of the effects of morphine and its analogues that have been described include the involvement of the central cholinergic system in the effects of morphine withdrawal 187 the effects of administration of reserpine and of amphetamine on the development of tolerance to morphine 188 the possible involvement of vitamin B6 in dependence on morphine 189 the loss of calcium from synaptosomes that is caused by morphine, and its reversal by nalorphine 190 the... 

Two new vitamin D analogues, maxacalcitol [29] and hexafluorocalcitriol [30] (Fig. 2.5) were designed to separate the antiproliferative effects of the natural hormone from its role in calcium and phosphate mobilization. There had not been... 

The immunosuppressive effects of 1,25-(OH)2D3 in such diseases as diabetes in non-obese diabetic (NOD) mice [375], and the autoimmune diseases murine lupus [376] and encephalomyelitis [377] reveal potentially important and novel uses for vitamin D treatment. However, it is clear that noncalce-mic immunopotent vitamin D analogues will have to be employed to prevent hypercalcaemia caused by 1,25-(OH)2D3. 

An analogue of vitamin A, isotretinoin (Accutane), or 13-cfs-retinoic acid, is used for control of severe recalcitrant cystic acne and other keratinizing dermatoses. Oral administration of 1 to 2 mg/kg body weight daily temporarily suppresses sebaceous gland activity, changes surfece lipid composition of the skin, and inhibits kera-tinization. The therapeutic effect is resolution of lesions and, in most patients, prolonged remission of the disease. 

It is known that a cooperative effect between LA and other natural antioxidants, such as tocopherol (vitamin E) or ascorbic acid, affords the possibility to reduce the formation of reactive oxygen species (ROS), associated with various pathological disorders. Thus triamine spacer as backbone was used to attach Trolox , a water-soluble analogue of vitamin E, and LA, to obtain new analogues 356 which were tested as inhibitors of the microsomal lipid peroxidation. Attachment of LA to the chroman moiety, as in compound 357, is a useful extension of this study <2001JME4300, 2004BMC4835>. 

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