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Hyper acetylation of histones increases the access of some transcription factors to nucleosomes thereby increasing RNA transcription. Histone deacetylase inhibitors HDI leads to hyper acetylation by blocking the function of histone deacetylase, therefore leaving the lysine amino acids acetylated from the histone acetyl transferase and ultimately increasing transcription. Keywords: Keyword Histone deacetylase inhibitors, Matrix metalloproteinase inhibitors, HIV, Hydroxamaates, Ribonucleoside diphosphate reductase Cite this paper: David I. The reasonable way of producing hydroxamic acid derivative is the reaction of hydroxylamine with acid chlorides or esters. 13 Hydroxamic acids are capable of inhibiting a variety of enzymes, including ureases, 14, 15 peroxidises 16, and matrix metalloproteinases. Ugwu, Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria. Abstract Hydroxamates are physiologically active compounds. They have found applications as histone deacetylase inhibitors widely applied in cancer treatment such as vorinostat, belinostat, panobinostat and trichostatin A. They are amides where the hydrogen H atom of NH center has been replaced by an OH. Hydroxamates are deprotonated product of hydroxamic acid and acts as excellent ligand. Ugwuja3 1Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria 2National Centre for Energy Research and Development, University of Nigeria, Nsukka, Nigeria 3Department of Chemical Sciences, Federal University, Wukari, Nigeria Correspondence to: David I. Introduction Hydroxamates are class of organic compounds bearing the functional group RICON OH RII as organic residues and CO as a carbonyl group.

Histone deacetylase are a group of enzymes that removes acetyl groups from the lysine residues on a histone. Oxidation of alcohol 24 under Swern condition 47 gave aldehyde 25 which was treated with an aryl Grignard reagent to produce alcohol 26. Alcohol 26 was treated with 2-methoxy propene and pyridinium p-toluenesulfonate PPTS to generate protected diol 27. This process increases the amount of RNA present in the cell and their respective encoded proteins. Synthesis of Trichostatin A Trichostatin A was the first naturally occurring HDI to be discovered. It causes an increase in acetylated histones in a variety of mammalian tumor cell line. 45 Trichostatin A was shown to be a selective histone deacetylase inhibitor, reversibly inhibiting classes I, II and IV types of HDAC while not affecting class III. 46 The first portion of the synthesis is shown in scheme 9.

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