No abstract

Te2(CF3)2 kristallisiert in der monoklinen Raumgruppe P21/a mit vier Formeleinheiten in der Elementarzelle. Die Gitterkonstanten betragen a = 10,13(1) Å, b = 11,489(7) Å, c = 6,822(8) Å und β = 101,20(8)°. Bei der Umsetzung von Te2(CF3)2 mit der äquimolaren Menge Iod entsteht CF3TeI in quantitativer Ausbeute, eine Isolierung gelingt nicht. Die NMR‐Spektren zeigen eine starke Lösungsmittelabhängigkeit. Durch Metathesereaktionen werden die Verbindungen CF3TeX (X = CCC6H5, t‐C4H9, SCN, SC6F5) synthetisiert.

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Leucinostatin Ai soneo ft he most potent antiprotozoal compounds ever described, but little was knowno n structure-activity relationships (SAR). We used Trypanosoma brucei as ap rotozoal model organism to test synthetically modified derivatives,r esulting in simplified but equally active compounds 2 (ZHAWOC6025) and 4 (ZHAWOC6027), which were subsequently modified in all regions of the molecule to gain an in-depth SAR understanding.T he antiprotozoal SAR matched SAR in phospholipid liposomes, where membrane integrity,l eaking, and dynamics were studied. The mode of action is discussed based on as tructure-activity analysis of derivatives in efficacy,u ltrastructural studies in T. brucei, and artificial membrane models,m imicking membrane stability and membrane potential. The main site of antiprotozoal action of natural and synthetic leucinostatins lies in the destabilization of the inner mitochondrial membrane,a sd emonstrated by ultrastructural analysis,e lectron microscopya nd mitochondrial staining.L ong-time sublethal exposure of T. brucei (200 passages) and siRNAs creening of 12'000 mutants showed no signs of resistance development to the synthetic derivatives.

Sentrin-specific proteases (SENPs) are responsible for the maturation of small ubiquitin-like modifiers (SUMOs) and the deconjugation of SUMOs from their substrate proteins. Studies on prostate cancer revealed an overexpression of SENP1, which promotes prostate cancer progression as well as metastasis. Therefore, SENP1 has been identified as a novel drug target against prostate cancer. Herein, we report the discovery and biological evaluation of potent and selective SENP1 inhibitors. A structure-activity relationship (SAR) of the newly identified pyridone scaffold revealed allosteric inhibitors with very attractive in vitro ADMET properties regarding plasma binding and plasma stability for this challenging target. This study also emphasizes the importance of biochemical mode of inhibition studies for de novo designed inhibitors.