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Rapid Access to Oxazine Fused Furocoumarins and in vivo and in silico Studies of theirs Biological Activity

[ Vol. 13 , Issue. 7 ]

Author(s):

Alla V. Lipeeva, Dmitry S. Baev, Margarita P. Dolgikh, Tatijana G. Tolstikova and Elvira E. Shults*   Pages 625 - 632 ( 8 )

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.

Keywords:

Analgesic activity, anti-inflammatory activity, furocoumarins, gold catalysis, molecular docking, oximes.

Affiliation:

Laboratory of Medicinal Chemistry, Novosibirsk Institute of Organic Chemistry, Siberian Branch, Novosibirsk, Novosibirsk State University, Novosibirsk, Laboratory of Pharmacological Researches, Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Laboratory of Pharmacological Researches, Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Laboratory of Medicinal Chemistry, Novosibirsk Institute of Organic Chemistry, P.O. Box: 630090, Novosibirsk

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