Lemke, Carina, Christmann, Joscha, Yin, Jiafei, Alonso, Jose M., Serrano, Estefania, Chioua, Mourad, Ismaili, Lhassane, Angeles Martinez-Grau, Maria, Beadle, Christopher D., Vetman, Tatiana, Dato, Florian M., Bartz, Ulrike, Elsinghorst, Paul W., Pietsch, Markus, Mueller, Christa E., Iriepa, Isabel ORCID: 0000-0003-3475-9624, Wille, Timo ORCID: 0000-0002-4359-5388, Marco-Contelles, Jose and Guetschow, Michael (2019). Chromenones as Multineurotargeting Inhibitors of Human Enzymes. ACS Omega, 4 (26). S. 22161 - 22169. WASHINGTON: AMER CHEMICAL SOC. ISSN 2470-1343

Full text not available from this repository.

Abstract

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 Mitsunobuor 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 mu M, respectively, was achieved with the dual-target 6-(4-(piperidin-1-yl)butoxy)-4H-chromen-4-one (7).

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lemke, CarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christmann, JoschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yin, JiafeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alonso, Jose M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Serrano, EstefaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chioua, MouradUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ismaili, LhassaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angeles Martinez-Grau, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beadle, Christopher D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vetman, TatianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dato, Florian M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartz, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elsinghorst, Paul W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietsch, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Christa E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iriepa, IsabelUNSPECIFIEDorcid.org/0000-0003-3475-9624UNSPECIFIED
Wille, TimoUNSPECIFIEDorcid.org/0000-0002-4359-5388UNSPECIFIED
Marco-Contelles, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guetschow, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-123975
DOI: 10.1021/acsomega.9b03409
Journal or Publication Title: ACS Omega
Volume: 4
Number: 26
Page Range: S. 22161 - 22169
Date: 2019
Publisher: AMER CHEMICAL SOC
Place of Publication: WASHINGTON
ISSN: 2470-1343
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MONOAMINE-OXIDASE B; ACETYLCHOLINESTERASE; DERIVATIVES; DISCOVERY; BUTYRYLCHOLINESTERASE; IDENTIFICATION; OPTIMIZATION; MATRIPTASE-2; MITSUNOBU; TARGETSMultiple languages
Chemistry, MultidisciplinaryMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12397

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item