Browsing Publications of the research group Chemical Biology (CBIO) by Authors
Novel peptidomimetic compounds containing redox active chalcogens and quinones as potential anticancer agents.Shaaban, Saad; Diestel, Randi; Hinkelmann, Bettina; Muthukumar, Yazh; Verma, Rajeshwar P; Sasse, Florenz; Jacob, Claus; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2012-12)Many types of cancer cells are associated with a disturbed intracellular redox balance and oxidative stress (OS). Among the various agents employed to modulate the intracellular redox state of cells, certain redox catalysts containing quinone and chalcogen moieties have shown considerable promise. Passerini multicomponent reaction has been developed for the synthesis of agents combining two, three or even four redox centers in one molecule in a good yield. When incubated with cancer cells these agents inhibited cell proliferation and induced apoptotic cell death. Interestingly, some of these redox active compounds exhibited quite low toxicity with normal cells. The cause was obviously OS, which was reflected by significant decrease in reduced glutathione, subsequently cell cycle arrest and induction of apoptosis.
Sulfur, selenium and tellurium pseudopeptides: synthesis and biological evaluation.Shaaban, Saad; Sasse, Florenz; Burkholz, Torsten; Jacob, Claus; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2014-07-15)A new series of sulfur, selenium and tellurium peptidomimetic compounds was prepared employing the Passerini and Ugi isocyanide based multicomponent reactions (IMCRs). These reactions were clearly superior to conventional methods traditionally used for organoselenium and organotellurium synthesis, such as classical nucleophilic substitution and coupling methods. From the biological point of view, these compounds are of considerable interest because of suspected anticancer and antimicrobial activities. While the sulfur and selenium containing compounds generally did not show either anticancer or antimicrobial activities, their tellurium based counterparts frequently exhibited antimicrobial activity and were also cytotoxic. Some of the compounds synthesized even showed selective activity against certain cancer cells in cell culture. These compounds induced a cell cycle delay in the G0/G1 phase. At closer inspection, the ER and the actin cytoskeleton appeared to be the primary cellular targets of these tellurium compounds, in line with some of our previous studies. As most of these peptidomimetic compounds also comply with Lipinski's Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations.