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The retinoids are a class of chemical compounds that are related chemically to vitamin A . Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth. Retinoids have many important and diverse functions throughout the body including roles in vision, regulation of cell proliferation and differentiation, growth of boneimmune function, and activation of tumor suppressor genes. tissue,
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| Vitamin A (Retinol) | all trans-Retinoic acid (ATRA) |
Retinoids have recently received considerable attention as agents, that may have utility for both cancer prevention and treatment due to their cell differentiation, proliferation and antioxidant effects. Additionally, retinoids have been shown to inhibit microsomal lipid peroxidation as effective antioxidants. The importance of antioxidants in the maintenance of health and in protection from the damage induced by oxidative stress (implicated in the risk of chronic diseases), is becoming to the forefront of mechanistic approaches to genetically originated diseases, which are related to retinoids. It is well known that cellular and subcellular membranes are susceptible to lipid oxidation because of their relatively high concentration of polyunsaturated fatty acids and close proximity to oxygen, transition metals, and peroxidases.
Therefore, there has been a great deal of interest in the study of reactive oxygen species (ROS) such as the superoxide anion, hydroxyl radical and hydrogen peroxide which are related to arteriosclerosis, nephritis and carcinogenesis. Clinically, natural retinoids such as all trans-retinoic acid (ATRA) and retinol (vitamin A) are used in the treatment of proliferative dermatological diseases and in the prevention of certain tumors. However, the applicability of retinoid remedy is limited due to toxic effects of natural retinoids. New retinoidal compounds that comprise specific acting properties on eliminating the reactive oxygen species, together with the lower toxic and/or side effects, could be useful for the precise treatment of above mentioned diseases, clinically. We have synthesized the synthesis and some antioxidant activities of novel benzimidazole retinoids which are structurally hybrid compounds between retinoic acid and benzimidazole moiety.
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alpha-Lipoic acid (1,2-dithione-3-pentanoic acid)
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We have synthesized several ALA derivatives for exploiding their antioxidant effects on different in vitro and in vivo systems. One of the most effective derivative among the synthesized compounds, is the hybrid one in which melatonin and ALA are integrated in a molecule. The antioxidant activity of this molecule is found twice than ALA itself. The radioprotection effect of this compound through whole body exposure, is under progress.
Melatonin, N-Acetyl-5-methoxytryptamine
Melatonin is a neurohormone, first isolated in 1958 from bovine pineal tissue, has a central role in the regulation of daily rhythms and seasonal cycles in vertebrates. Its potential usefulness to a number of therapeutic areas such as those related to the desynchronization of biological rhythms, such as jet-lag, disturbed sleep-wake cycles, seasonal disorders and depression are known. Melatonin may also play a role in the cardiovascular system. This is supported by recent findings which show that 2-[125I] iodomelatonin-binding sites are localized in both the caudal and cerebral arteries of the rat. In addition, melatonin binding has been reported at many other sites including the retina (probably related to resynchronization role) and peripheral tissues such as the spleen (related to a role immune system), gastrointestinal tract, blood platelets and the harderian gland. Furthermore antioxidant properties of melatonin have recently been proposed. Although the effects of melatonin in oncogenesis are unclear; majority of the studies conclude that the hormone has a protective role in the modulation of cancer or cancerous cells. Melatonin may also play a role in brain function, but the mechanisms underlying such functions are yet not known.
Despite its potential involvement in the regulation in many possible physiological processes, two problems limit its therapeutic use at present. The first is, its very short biological half-life (15-30 min), due to its rapid metabolism to 6-hydroxymelatonin and N-acetylkynurenamines, and second is the lack of selectivity of melatonin at target sites. It is thought that the development of novel analogues may provide a strategic approach to overcome both of these limitations. Therefore, we have synthesized novel melatonin derivatives and investigate their antioxidant capacities.
Drug design and discovery is a powerful, time-consuming and an interdisciplinary effort and is mostly defined as a straight, consecutive progress that includes the definition of targets (mostly proteins) and lead discovery. The optimization of selected lead compound requires pre-clinical in vitro and in vivo studies to resolve wheather the compound is emerged to fulfill most of the pre-set criteria for initiating clinical requirements.
In the earlier decades, most drugs have been discovered in random findings. However, computers (in-silico design) and appropriate new techniques are now being available for rational approaches to design and development of novel drugs.
1. I am lost in LOST!
2. STAR TREK, ...to seek out new life and new civilizations... to boldly go...WHERE NO MAN HAS GONE BEFORE...
I’m addicted to Star Trek in all of its constitutes.
The affirmation of a positive future for the human race, the faith in the human intellect will soon overcome new and challenging environments.