TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - Lemke, Carina A1 - Christmann, Joscha A1 - Yin, Jiafei A1 - Alonso, José M. A1 - Serrano, Estefanía A1 - Chioua, Mourad A1 - Ismaili, Lhassane A1 - Martínez-Grau, María Angeles A1 - Beadle, Christopher D. A1 - Vetman, Tatiana A1 - Dato, Florian M. A1 - Bartz, Ulrike A1 - Elsinghorst, Paul W. A1 - Pietsch, Markus A1 - Müller, Christa E. A1 - Iriepa, Isabel A1 - Wille, Timo A1 - Marco-Contelles, José A1 - Gütschow, Michael T1 - Chromenones as Multineurotargeting Inhibitors of Human Enzymes JF - ACS Omega N2 - The complex nature of multifactorial diseases, such as Morbus Alzheimer, has produced a strong need to design multitarget-directed ligands to address the involved complementary pathways. We performed a purposive structural modification of a tetratarget small-molecule, that is contilisant, and generated a combinatorial library of 28 substituted chromen-4-ones. The compounds comprise a basic moiety which is linker-connected to the 6-position of the heterocyclic chromenone core. The syntheses were accomplished by Mitsunobu- or Williamson-type ether formations. The resulting library members were evaluated at a panel of seven human enzymes, all of which being involved in the pathophysiology of neurodegeneration. A concomitant inhibition of human acetylcholinesterase and human monoamine oxidase B, with IC50 values of 5.58 and 7.20 μM, respectively, was achieved with the dual-target 6-(4-(piperidin-1-yl)butoxy)-4H-chromen-4-one (7). UN - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-47081 SN - 2470-1343 SS - 2470-1343 U6 - https://doi.org/10.1021/acsomega.9b03409 DO - https://doi.org/10.1021/acsomega.9b03409 PM - 31891098 VL - 4 IS - 26 SP - 21636 EP - 22260 PB - American Chemical Society (ACS) ER -