Multicomponent reactions for the synthesis of multifunctional agents with activity against cancer cells

Abstract

Multicomponent Passerini and Ugi reactions enable the fast and efficient synthesis of redox-active multifunctional selenium and tellurium compounds, of which some show considerable cytotoxicity against specific cancer cells.

Sulfur, selenium and tellurium pseudopeptides: Synthesis and biological evaluation

“…We have already shown that the quinone containing chalcogen compounds (3, 4, 5 and 6) exert their main cytotoxic effects at least in part via modulation of the intracellular redox state. 13 Consequently, these compounds were able to inhibit cancer cell proliferation by induction of Oxidative Stress, cell cycle delay, alteration of the cytoskeleton and apoptosis. 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.…”

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.…”

“…Chalcogens (sulfur, selenium and tellurium) bearing isonitriles have therefore been synthesized accordingly to overcome this sophisticated limitation. 13 Based on these results, we are now interested to further explore the reactivity of these isonitriles and to generate a library of diverse and highly functionalized organochalcogens of expected biological activity.…”

“…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 ).…”

“…TLC plates (silica gel 60 F 254 , 0.20 mm) were purchased from Merck (Germany). NMR Spectroscopy: 1 H NMR spectra were recorded at 500 MHz, 13 C NMR spectra at 125 MHz on a Bruker DRX 500 or Avance 500 spectrometer. Chemical shifts are reported in δ (ppm), expressed relative to the solvent signal at 7.26 ppm (CDCl 3 , 1 H NMR) and at 77.16 ppm (CDCl 3 , 13 C NMR), as well as 3.31 ppm ( 1 H NMR, CD 3 OD) and 49.00 ppm ( 13 C NMR, CD 3 OD).…”