RESUMO
The hydroxamic acid functionality, a histone deacetylase inhibitor, has received much attention in relation to its physiological properties. This review mainly deals with the chemistry, mechanism, cell signaling, therapeutic properties, clinical trials, and toxicity. The chemistry provides insight concerning the mechanism. Acyl nitroso apparently is an intermediate, based on ease of oxidation of the parent and subsequent formation of nitroxyl (HNO) and nitric oxide. Acyl nitroso bears structural and electrochemical similarity to the phenylhydroxylamine-nitrosobenzene couple and to α-dicarbonyls. Acyl nitroso may be involved in electron transfer, reactive oxygen species formation and oxidative stress. Cell signaling plays a significant role in the biological action. The therapeutic properties are discussed with suberoylanilide hydroxamic acid attracting the most attention as an anticancer agent. Promise as a practical medicine for treatment of cancer is indicated by clinical trials. Toxicity is also included. Acyl nitroso, HNO, nitric oxide, and metal complexes of the parent drug are designated the main actors in the physiological effects.
