Small Molecule Catalysts with Therapeutic Potential

Abstract

Catalysts are employed in many areas of research and development where they combine high efficiency with often astonishing selectivity for their respective substrates. In biology, biocatalysts are omnipresent. Enzymes facilitate highly controlled, sophisticated cellular processes, such as metabolic conversions, sensing and signalling, and are prominent targets in drug development. In contrast, the therapeutic use of catalysts per se is still rather limited. Recent research has shown that small molecule catalytic agents able to modulate the redox state of the target cell bear considerable promise, particularly in the context of inflammatory and infectious diseases, stroke, ageing and even cancer. Rather than being “active” on their own in a more traditional sense, such agents develop their activity by initiating, promoting, enhancing or redirecting reactions between biomolecules already present in the cell, and their activity therefore depends critically on the predisposition of the target cell itself. Redox catalysts, for instance, preferably target cells with a distinct sensitivity towards changes in an already disturbed redox balance and/or increased levels of reactive oxygen species. Indeed, certain transition metal, chalcogen and quinone agents may activate an antioxidant response in normal cells whilst at the same time triggering apoptosis in cancer cells with a different pre-existing “biochemical redox signature” and closer to the internal redox threshold. In pharmacy, catalysts therefore stand out as promising lead structures, as sensor/effector agents which are highly effective, fairly selective, active in catalytic, i.e., often nanomolar concentrations and also very flexible in their structural design.

Antioxidant activity evaluation of derivatives with 6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine scaffold

“…This field, therefore, attracts ever-growing interest in the modern drug discovery experts [10]. So far, the free radical scavengers [11], "multipotent" antioxidants [12], "sensor/effector agents" [13] and "redox cyclers" [14] have been designed and are currently studied as new opportunities and strategies for the treatment of OS-associated disorders as well as potential prevention/delay of aging. {{Since redox dysregulations are widely spread among multiple types of diseases and are not limited to cancer, inflammation and infectious diseases, there are many reasons to believe those novel drug molecules capable to selectively modulating the intensity of ROS production enhance the utilization or activation/inhibition of redox-sensitive enzymes may provide new avenues to tackle OS-related diseases and improve their treatments.…”

Stereoselective Reduction of Alkynes: Synthesis of 4-Organoselenyl Quinolines

“…The versatility of the carbon–selenium bond makes organoselenium compounds a powerful tool to provide several new bonds such as carbon–carbon, carbon–lithium, carbon–halogen, and carbon–hydrogen bonds, among others. They also have a wide application as catalysts; as useful substrates for the synthesis of natural products; and in other fields such as biology, agriculture, chemistry, and medicine . The organoselenium compounds can be used as synthetic tools to prepare several new compounds; however, if necessary, they can also be easily removed from the structure under mild conditions using, for example, selenoxide elimination.…”