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.

Synthesis of Functionalised Chromonyl‐pyrimidines and Their Potential as Antimycobacterial Agents

“…Next, the synthesis of the 2‐substituted amino‐chromones ( IV ) was undertaken whereby 2′‐hydroxyacetophenone ( 10 ) was first subjected to Kostanecki conditions to give ethyl ester 11 , which was then nitrated to give 6‐nitro‐chromone 12 in 90% yield over the two steps (Scheme ) . A Claisen condensation between acetophenone 10 and ethyl cyclopropane‐carboxylate then afforded chromone 13 , which after nitration gave cyclopropyl‐substituted nitro‐chromone 14 in 65% yield over the two steps.…”

Mast cell stabilisers

“…Within the analogues synthesised, the most important structural feature appeared to be the pattern of hydroxylation of positions 6 and 2' of the 3-phenylcoumarins, in addition to catechol, amino and thiophene moieties. Work on photoswitchable chromone dimers based on cromolyn sodium, where the non chromone part was replaced by azo/azobenzene spacer groups, revealed interesting preliminary data on three compounds tested as to the effect on activity of changing their cis:trans ratio following photoisomerisation (Velema et al, 2013). The mast stabilising data generated was sparse stemming from the low number of compounds evaluated, the use of only one cell line (LAD2) and only using compound 48/80 as elicitor.…”

Isatin N2-diphenylhydrazones: new easily synthesized Vis-Vis molecular photoswitches

“…These include nucleic acid structure and function, transcription and translation, protein folding, enzyme activity, protein−ligand interactions, peptide structure and function, membrane transport, and receptor modulation and signalling [22,23]. Light is an ideal external control for in situ chemical and biological manipulation.…”