Synthesis, structure elucidation, DNA-PK, PI3K, anti-platelet and anti-bacteria activity of linear 5, 6, and 10-substituted-2-morpholino-chromen-oxazine-dione and angular 3, 4, 6-substituted-8-morpholino-chromen-oxazine-2,10-dione

Abstract

Coumarin, a naturally occurring or synthesised phytochemical, displays a wide range of biological activities. However, chromen-2-ones fused with 1,3-benzoxazine rings is not well documented and there is a gap in the literature which required engaging. The substituted-2-thioxo-chromen-oxazine linear compounds 14a–i and angular compounds 16a–e were synthesised from the reaction of hydroxy-substituted-chromene-carboxylic 10–13 with freshly prepared Ph₃P(SCN)₂. 2-Morpholino-substituted-chromen-oxazine-4,8-dione and 8-morpholino-substituted-chromen-oxazine-2,10-dione 15a–f and 17 were synthesised from the reaction of the corresponding oxazines 14 and 16 with morpholine. PI3K activity was observed for the hydroxy-substituted-chromene-carboxylic acid of which compound 13b showed moderate PI3Kγ (IC₅₀=5.56 μM) and PI3Kα (IC₅₀=14.7 μM) activity. Additionally, 8-morpholino-chromen-oxazine-2,10-dione 17a showed isoform selective PI3Kδ activity with IC₅₀=5.08 μM with non-DNA-PK ≥ 100 μM. Consequently compound 17a can be considered as a selective PI3Kδ inhibitor with non-DNA-PK at compound concentrations ≥100 μM.

Keywords:

• Anti-bacterial activity
• anti-platelet
• DNA-PK
• PI3K
• morpholino-chromen[1,3]oxazines

Declaration of interest

The authors declare no conflict of interest.

Supplementary material available online