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Despite much research and undeniable advances, cancer treatment and prevention has remained a major challenge for scientists. Both genetic and epigenetic changes are involved in the growth and development of cancer complex and multifactorial disease. Among the possible treatment options, multidrug epigenetic therapy such as the use of dual epigenetic inhibitors, has been a popular option in recent years. Histone deacetylases (HDACs) as epigenetic eraser and bromodomain-containing protein 4 (BRD4) as epigenetic reader are epigenetic modifiers, which are rapidly being investigated. Using of a single molecule that simultaneously targets HDACs and BRD4 has been recently employed by medicinal chemists. Presently, there are no approved BRD4 inhibitor and dual BRD4/HDAC inhibitor in the drug market but evidence suggests their possible therapeutic potential in various diseases, such as cancer. In this review, the overall structure of the synthesized dual BRD4/HDAC small molecule inhibitors, lead compounds, and the biological and pharmacological properties of the most potent dual BRD4/HDAC inhibitor in each category are all collected in the hopes of assisting in the development of stronger and more selective dual BRD4/HDAC inhibitors in future studies.

The Doebner reaction is the chemical reaction of an aniline with an aldehyde and pyruvic acid to form quinoline-4-carboxylic acids. Although Doebner reaction is a simple procedure for synthesis of ...

HDAC inhibitors and NO donors have both demonstrated independently broad therapeutic potential in a variety of diseases. Borretto et al. presented the topic of NO-HDAC dual inhibitors for the first time in 2013 as an attractive new topic. Here we collected the general structure of all synthesized NO-HDAC dual inhibitors, lead compounds, synthesis methods and biological features of the most potent dual NO-HDAC inhibitor in each category with the intention of assisting in the synthesis and optimization of new drug-like compounds for diverse diseases. Based on studies done so far, NO-HDAC dual inhibitors have displayed satisfactory results against wound healing (3), heart hypertrophy (3), inflammatory, cardiovascular, neuromuscular illnesses (11a-11e) and cancer (6a-6o, 9a-9d, 10a-10d, 16 and 17). NO-HDAC dual inhibitors can have high therapeutic potential for various diseases due to their new properties, NO properties, HDAC inhibitor properties and also due to the effects of NO on HDAC enzymes.