0000000000723420
AUTHOR
Katrin Fischer
Identification of 2-(thiophen-2-yl)acetic Acid-Based Lead Compound for mPGES-1 Inhibition.
We report the implementation of our in silico/synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the Suzuki-Miyaura reaction, we identified 3-phenylpropanoic acid and 2-(thiophen-2-yl)acetic acid to be suitable chemical platforms to develop tighter mPGES-1 inhibitors. Among these, compounds 1c and 2c showed selective inhibitory activity against mPGES-1 in the low micromolar range in accordance with molecular modeling calculations. Moreover, 1c and 2c exhibited interesting IC…
Homoseksualitāte Tomasa Manna darba "Nāve Venēcijā"
Tomasa Manna romāna Nāve Venēcijā galvenā varoņa Gustava fon Ašenbaha iekšējā drāma ir viena no noveles galvenajām interesēm. Varonis tiek attēlots kā izcils vācu rakstnieks nobriedušā vecumā, kurš ierodas Itālijas pilsētā Venēcijā un pēkšņi viņu apsēdis daudz jaunāks vīrietis, kamēr varonis bēgot piedzīvo krīzi, sevis atklāšanu un galu galā iznīcību. Savā darbā es vēlos koncentrēties uz homoerotismu un galvenā varoņa pederastikas tēmu. Manā darbā tiks ņemta vērā homoerotisma vēsturiskā poētika, Gustava fon Ašenbaha dzīve un viņa ceļojuma uz Venēciju analīze. Interesanti, ka šogad aprit tieši 110 gadi kopš romāna izdošanas. Lai gan romānā publicētā darba esamība nav tik šokējoša kā tā iznāk…
2,3-Dihydrobenzofuran privileged structures as new bioinspired lead compounds for the design of mPGES-1 inhibitors
International audience; 2,3-Dihydrobenzofurans are proposed as privileged structures and used as chemical platform to design small compound libraries. By combining molecular docking calculations and experimental verification of biochemical interference, we selected some potential inhibitors of microsomal prostaglandin E2 synthase (mPGES)-1. Starting from low affinity natural product 1, by our combined approach we identified the compounds 19 and 20 with biological activity in the low micromolar range. Our data suggest that the 2,3-dihydrobenzofuran derivatives might be suitable bioinspired lead compounds for development of new generation mPGES-1 inhibitors with increased affinity.