Incorporating Selenium into Heterocycles and Natural Products─From Chemical Properties to Pharmacological Activities

Abstract

Selenium (Se)-containing compounds have emerged as potential therapeutic agents for the treatment of a range of diseases. Through tremendous effort, considerable knowledge has been acquired to understand the complex chemical properties and biological activities of selenium, especially after its incorporation into bioactive molecules. From this perspective, we compiled extensive literature evidence to summarize and critically discuss the relationship between the pharmacological activities and chemical properties of selenium compounds and the strategic incorporation of selenium into organic molecules, especially bioactive heterocycles and natural products. We also provide perspectives regarding the challenges in selenium-based medicinal chemistry and future research directions.

Clickable Selenylation – a Paradigm for Seleno‐Medicinal Chemistry

“…However, only rare methods have been reported for the construction of Org‐Se compound libraries up to now. Therefore, the development of selenylation chemistries that suitable for parallel synthesis of Org‐Se library and/or Se‐containing DNA‐encoded library ( Se DEL) are highly needed for the development of seleno‐medicinal chemistry [9,10] …”

“…Notably, accumulated evidence in chemical biology and medicinal chemistry has indicated that the special chemical properties of Se play a key role in the pharmacological activity, toxicity and metabolic property of Org-Se compounds. [3,9,10] The incorporation of Se into small molecules or natural products have been reported to bring additional benefits, which are closely correlated with the specific Se species as well as their ability to modulate the oxidative stress status of cells, mainly including antioxidation and prooxidation (Figure 1). [9,10] All of these merits indicate the versatile ability of Se in medicinal chemistry.…”

“…[3,9,10] The incorporation of Se into small molecules or natural products have been reported to bring additional benefits, which are closely correlated with the specific Se species as well as their ability to modulate the oxidative stress status of cells, mainly including antioxidation and prooxidation (Figure 1). [9,10] All of these merits indicate the versatile ability of Se in medicinal chemistry. However, the research on Org-Se therapeutic agents is still in its infancy at present, the lack and lag of efficient synthetic toolbox to access a large chemical space of Org-Se compounds is one of the key bottle necks.…”

“…Therefore, the development of selenylation chemistries that suitable for parallel synthesis of Org-Se library and/or Se-containing DNA-encoded library (SeDEL) are highly needed for the development of seleno-medicinal chemistry. [9,10] In this concept, we analyzed the established click chemistries that can be used for parallel synthesis of compound libraries, which are suitable for in situ biological activity screening. We paid special attention on the clickable selenylation reaction, and the DNA compatible selenylation chemistries that have been developed for SeDEL synthesis.…”

Discovery of Novel Bicyclic Phenylselenyl-Containing Hybrids: An Orally Bioavailable, Potential, and Multiacting Class of Estrogen Receptor Modulators against Endocrine-Resistant Breast Cancer

“…As a crucial component of selenoprotein, selenium (Se) is implicated in numerous cellular physiological processes and is crucial for human health and disease. − In recent years, growing interest has been paid to Se-containing compounds due to their therapeutic potential against cancer and other diseases by modulating cellular redox status. Se-containing compounds as anticancer agents (such as Ebselen, 2 ) possess pro-oxidative capabilities at higher concentrations, and there is evidence for their high efficiency and selectivity to cancer cells. − The arylselenium compounds, such as phenylselenide, represent a group of simple anticancer molecules. Significant evidence was provided that the introduction of phenylselenyl (PhSe) into small molecules was beneficial for modulating their redox ability, enhancing their uptake, improving their efficacy, and antagonizing drug resistance. − The hybrid compounds ( 3 ) consisting of PhSe and quinone redox centers exhibited a significant and selective antineoplastic activity through increasing ROS levels to alter the redox levels of cancer cell. − Hydantoin derivative ( 4) with a PhSe tail displayed more potent inhibitory activities in resistant T-lymphoma cells probably due to PhSe moiety .…”