Synthesis and biological evaluation of simplified ajudazol derivatives reveal potent 5-lipoxygenase inhibition and considerable apoptotic activity in neuroblastoma cells

Philipp Wollnitzke; Raphael Wagner; Sumaiya Yasmeen Afsar; Markus Werner; Robin Geschold; Christa E Müller; Oliver Werz; Gerhild van Echten-Deckert; Dirk Menche

doi:10.1016/j.bmcl.2023.129464

Synthesis and biological evaluation of simplified ajudazol derivatives reveal potent 5-lipoxygenase inhibition and considerable apoptotic activity in neuroblastoma cells

Bioorg Med Chem Lett. 2023 Oct 1:94:129464. doi: 10.1016/j.bmcl.2023.129464. Epub 2023 Aug 25.

Authors

Philipp Wollnitzke¹, Raphael Wagner¹, Sumaiya Yasmeen Afsar², Markus Werner³, Robin Geschold⁴, Christa E Müller⁴, Oliver Werz³, Gerhild van Echten-Deckert⁵, Dirk Menche⁶

Affiliations

¹ Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany.
² Life & Medical Science (LIMES) Institute for Membrane Biology and Lipid, Biochemistry at the Kekulé-Institute, University of Bonn, 53121 Bonn, Germany.
³ Department of Pharmaceutical and Medicinal Chemistry Institute of Pharmacy, Friedrich Schiller University Jena, Philosophenweg 14, 07743 Jena, Germany.
⁴ Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, Universität Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
⁵ Life & Medical Science (LIMES) Institute for Membrane Biology and Lipid, Biochemistry at the Kekulé-Institute, University of Bonn, 53121 Bonn, Germany. Electronic address: g.echten.deckert@uni-bonn.de.
⁶ Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany. Electronic address: dirk.menche@uni-bonn.de.

PMID: 37634760
DOI: 10.1016/j.bmcl.2023.129464

Abstract

Simplified analogues of the myxobacterial polyketide ajudazol were obtained by synthesis and evaluated for their biological activities. Potent simplified 5-lipoxygenase inhibitors were identified. Moreover, strong antiproliferative and apoptotic activities were observed in brain cancer cell lines at low nano- to micromolar concentrations.

Keywords: Ajudazol; Anti-inflammatory activity; Derivative; Neuroblastoma cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arachidonate 5-Lipoxygenase
Brain Neoplasms*
Cell Line
Humans
Lipoxygenase Inhibitors* / chemistry
Lipoxygenase Inhibitors* / pharmacology
Neuroblastoma* / drug therapy

Substances

Arachidonate 5-Lipoxygenase
ajudazol A
ajudazol B
Lipoxygenase Inhibitors