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.
HDAC performs the reverse process of histone acetyl co A to the lysines on the histone, inducing a state known as hyper acetylation.
Hyper acetylation causes a decreased binding of the histones to DNA and leads to chromatin expansion, allowing transcription to take place.
Removal of the acetyl groups known as hypo acetylation restores the normal positive change to the histone and therefore allows the DNA to condense and prevent transcription.
This silencing can become permanent if the unprotected lysines are then methylated.
17, 18 These class of compounds are used in the design of therapeutics targeting cancer 19, 20 e.g.
29 The wide biological application of hydroxamates necessitates the review of its synthesis and biological applications. General Synthesis of Weinreb Amides Hydroxamic acids are prepared usually from esters or acid chlorides or carboxylic acids.2.1.
The syntheses of various classes of hydroxamates and their mode of biological applications have been reviewed. 4 Much of their activities are due to their chelating properties with metal ions, especially with transition metals, hence constituting a very important class of chelating agents with versatile biological activities.
The broad biological activities of hydroxamates and the need to improve on their synthetic routes informed the review of their synthesis and biological applications. 5, 6 A number of synthetic routes are available for the preparation of hydroxamic acids, 7-12 but some are tedious, time consuming and costly as well. Colombo, An improved synthesis of the HDAC inhibitorn trichostatin A, Master s Theses and Doctoral Dissertations, Eastern Michigan University, 2009, 1-2.
Synthesis of Benzohydroxamic Acid 3 The synthesis of compound 3 was achieved by reacting methyl benzoate 1 and hydroxylamine 2. Synthesis of Hydroxamates Using N, N1, NII–trimethoxy-N, NI, NII-trimethyl Phosphorus Triamides 5 Nui et al 31 reported the conversion of aromatic and aliphatic carboxylic acids, including sterically hindered substrates directly to hydroxamates using N, NI, NII-trimethoxy-N, NI, NII–trimethyl phosphorus triamide 5.
On condensation of aromatic or aliphatic carboxylic acid 4 0.01M and compound 5 0.005M in toluene at 60 for 0.5 to 1 h, the hydroxamate 6 was obtained in excellent yield. Ester Synthesis of Hydroxamate Riva et al 32 reported the transformation of methyl or ethyl carboxylic esters into the corresponding hydroxamic acid.