Title:Rapid Access to Oxazine Fused Furocoumarins and in vivo and in silico Studies of theirs Biological Activity
Volume: 13
Issue: 7
Author(s): Alla V. Lipeeva, Dmitry S. Baev, Margarita P. Dolgikh, Tatijana G. Tolstikova and Elvira E. Shults*
Affiliation:
- Laboratory of Medicinal Chemistry, Novosibirsk Institute of Organic Chemistry, P.O. Box: 630090, Novosibirsk,Russian Federation
Keywords:
Analgesic activity, anti-inflammatory activity, furocoumarins, gold catalysis, molecular docking, oximes.
Abstract: Background: The synthesis of 1,2-oxazine-fused linear furocoumarins was performed involving
the transition metal catalysis reaction of plant coumarin oreoselone derivatives.
Objective and Method: The Pd-catalyzed desulfonative cross-coupling reactions of 2-(tosyl)oreoselone
with terminal alkynes and the successive treatment of the obtained 2-(arylethynyl)furocoumarins with an
excess of hydroxylamine gave the expected (Z,E)-3-(hydroxyimino)-2-(arylethynyl)furocoumarins with
an (Z:E) ratio of about 1:0.5. The gold(III)-catalyzed cycloisomerization of furocoumarin β,γ-acetylenic
(Z)-oximes led to a new group of heterocyclic compounds - chromeno[6',7':4,5]furo[3,2-c][1,2]oxazine.
The (E)-isomer in this condition was transformed into (E)-3-(hydroxyimino)-2-(propan-2-ylidene)
furocoumarin.
Results: Pharmacological screening of the synthesized 1,2-oxazine-fused linear furocoumarins for
anti-inflammatory and analgesic activity in vivo revealed that this compounds possessed high activity
which was depend on the substitution in the aromatic ring of the oxazine unit. The results of experimental
studies were found to be in accordance with that of the in silico docking results.
Conclusion: The moderate toxicity of compounds (LD50 value was more than 2000 mg/kg) encouraged
the further design of therapeutically relevant analogues based on this novel type of fused linear furocoumarins.
