The Effect of Organoselenium Compounds on Histone Deacetylase Inhibition and Their Potential for Cancer Therapy

Genetic and epigenetic changes alter gene expression, contributing to cancer. Epigenetic changes in cancer arise from alterations in DNA and histone modifications that lead to tumour suppressor gene silencing and the activation of oncogenes. The acetylation status of histones and non-histone proteins are determined by the histone deacetylases and histone acetyltransferases that control gene transcription. Organoselenium compounds have become promising contenders in cancer therapeutics. Apart from their anti-oxidative effects, several natural and synthetic organoselenium compounds and metabolites act as histone deacetylase inhibitors, which influence the acetylation status of histones and non-histone proteins, altering gene transcription. This review aims to summarise the effect of natural and synthetic organoselenium compounds on histone and non-histone protein acetylation/deacetylation in cancer therapy.

Urea-functionalized organoselenium compounds as promising anti-HepG2 and apoptosis-inducing agents

Hepatocellular carcinoma is a highly aggressive and difficult-to-treat type of cancer. Incorporating urea functionality into the backbone of organoselenium compounds is expected to develop promising chemotherapeutic leads against liver cancer. Methods: Urea-functionalized organoselenium compounds were synthesized in good yields, and their cytotoxicity was evaluated against HepG2 cells. Results: 1,1′-(Diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) exhibited efficient anti-HepG2 activity in sub-micromolar concentrations, with no toxicity to normal human skin fibroblasts. The molecular mechanisms of the diselenide-based urea 14 were evaluated using colony formation, wound healing, 3D spheroid invasion assays, cell cycle analysis and apoptosis induction. Its redox properties were also assessed by using different bioassays. Conclusion: Our study revealed promising anticancer, antimigratory and anti-invasiveness properties of 1,1′-(diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) against HepG2.

Regioselective C–H selenylation of heteroarenes under metal-free conditions

Selenium-containing heteroarenes consist of a synthetically valuable family of compounds that found applications in many different areas, such as organic synthesis, medicinal chemistry, supramolecular chemistry, and optoelectronic devices construction. Over the past decade, many advances have been achieved to the synthesis of these substances, and this review aims to cover a literature survey of the direct selenylation of heteroarenes under metal-free conditions, which represents one of the most powerful synthetic strategies for the preparation of those target molecules. The construction of new C-Se bonds through selective C-H functionalization reactions has become useful and atom-economical. The widespread adoption of metal-free approaches has emerged as versatile, sustainable, and safe access to these organoselenium compounds. Among the features of these new protocols are the use of mild oxidants and halogen-based catalysts, inorganic bases, as well as photo-induced reactions, and electrosynthesis.

Diselenides and Selenocyanates as Versatile Precursors for the Synthesis of Pharmaceutically Relevant Compounds

: Organoselenium chemistry has undergone extensive development during the past decades, mostly due to the unique chemical properties of organoselenium compounds that have been widely explored in a number of synthetic transformations, as well as due to the interesting biological properties of these compounds. Diselenides and selenocyanates constitute the promising classes of organoselenium compounds that possess interesting biological effects and that can be used in the preparation of other selenium compounds. The combination of diselenide and selenocyanate moieties with other biologically relevant molecules (such as heterocycles, steroids, etc.) is a way for the development of compounds with promising pharmaceutical potential. Therefore, the aim of this review is to highlight the recent achievements in the use of diselenides or selenocyanates as precursors for the synthesis of pharmaceutically relevant compounds, preferentially compounds with antitumor and antimicrobial activities.