title: Design, synthesis, and inhibitory activity of potent, photoswitchable mast cell activation inhibitors.
abstract: Allergic reactions affect millions of people worldwide. The need for new and effective antiallergic agents is evident, and insight into the underlying mechanisms that lead to allergic events is necessary. Herein, we report the design, synthesis, and activity of photoswitchable mast cell activation inhibitors. In mast cell degranulation assays, these inhibitors possess significantly greater potency than an original, chromone-based antiallergic agent. Furthermore, one of the photoswitchable inhibitors shows a significant difference in inhibitory activity between its two photoisomeric forms. Further optimization could ultimately lead to a photoswitchable compound suitable for studying mechanisms involved in allergic reactions in a novel manner, with activity addressable by light and with precise spatiotemporal control over events at the molecular level.
authors.affiliation: Centre for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Velema
authors.forename: Marco
authors.initials: M
authors.lastname: van der Toorn
authors.forename: Wiktor
authors.initials: W
authors.lastname: Szymanski
authors.forename: Ben L
authors.initials: BL
authors.lastname: Feringa
mesh_terms: D018926:Anti-Allergic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001391:Azo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015550:Cell Degranulation; D002460:Cell Line; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008027:Light; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors
chemical_list: D018926:Anti-Allergic Agents; D001391:Azo Compounds; D002867:Chromones; C582915:diazochromone; C582916:meta-azochromone; C582917:para-azochromone; D001619:beta-N-Acetylhexosaminidases