Exploring synthetic avenues for the effective synthesis of selenium- and tellurium-containing multifunctional redox agents

Abstract

Various human illnesses, including several types of cancer and infectious diseases, are related to changes in the cellular redox homeostasis. During the last decade, several approaches have been explored which employ such disturbed redox balances for the benefit of therapy. Compounds able to modulate the intracellular redox state of cells have been developed, which effectively, yet also selectively, appear to kill cancer cells and a range of pathogenic microorganisms. Among the various agents employed, certain redox catalysts have shown considerable promise since they are non-toxic on their own yet develop an effective, often selective cytotoxicity in the presence of the 'correct' intracellular redox partners. Aminoalkylation, amide coupling and multicomponent reactions are suitable synthetic methods to generate a vast number of such multifunctional catalysts, which are chemically diverse and, depending on their structure, exhibit various interesting biological activities.

Sulfur, selenium and tellurium pseudopeptides: Synthesis and biological evaluation

“…Furthermore, we have also shown that the tellurium containing compounds 6 and 5 are generally able to enhance the oxidation of thiols in the presence of H 2 O 2 , using a simple in vitro thiophenol oxidation assay. 11,12 In continuation of our previous work, the ROS levels in (the more robust) A 431 cells were monitored using the standard fluorescent 2`, 7` dichlorodihydrofluorescin diacetate (DCHFA) assay, which can be considered as a general ROS indicator, as DCHFA reacts readily with most common ROS, including H 2 O 2 , lipid hydroperoxides and ONOO − . 17 As suspected, in the concentration range used, sulfur and selenium based compounds were unable to disturb the ROS levels in A 431 melanoma cells over a 1 h treatment period.…”

Novel peptidomimetic compounds containing redox active chalcogens and quinones as potential anticancer agents

“…As before, the IMCR-based approach turned out to be rather successful for the synthesis of a range of chemically diverse sulfur-, selenium-and tellurium-containing peptidomimetic compounds (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). These compounds were tested in various cancer cell lines and, in the case of the tellurium compounds, showed considerable activity in many of these cell cultures, possibly by selectively damaging the ER and actin cytoskeleton, delaying the cell cycle and inducing apoptosis.…”

“…11,12 Although the method appears to work well, the scope of the method is rather limited by the accessibility to the isonitrile building block. Chalcogens (sulfur, selenium and tellurium) bearing isonitriles have therefore been synthesized accordingly to overcome this sophisticated limitation.…”

“…As far as the chemical synthesis is concerned, readily available building blocks, including isonitriles were used in the Passerini and Ugi MCRs for the synthesis of 18 peptidomimetic compounds (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) (Figure 2). The individual building blocks used are shown in Figure 1, whereby the isonitriles were prepared in a good yield (up to 82 %) by dehydration of their corresponding formamides using phosphoryl chloride (POCl 3 ).…”

Chemical Biology: What is Its Role in Drug Discovery?

“…A library of cyclic pentapeptides were synthesised as potential antagonists of CXCR4, a member of the G-protein coupled receptor family, which is implicated in many diseases including cancer . Redox catalysts containing selenium and tellurium have been designed and synthesised since compounds with the ability to alter the redox state in cells have potential anti-cancer activity (Mecklenburg et al, 2009). A number of the compounds prepared possess interesting biological activities.…”