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

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

Journal

Medicinal Chemistry
ISSN: 1573-4064 , E-ISSN: 1875-6638

Output data

Year: 2017, Volume: 13, Number: 7, Pages: 625-632 Pages count : DOI: 10.2174/1573406413666170601114527

Tags

Analgesic activity; anti-inflammatory activity; furocoumarins; gold catalysis; molecular docking; oximes

Authors

Lipeeva Alla V. ^1,2 , Baev Dmitry S. ^3,4 , Dolgikh Margarita P. ³ , Tolstikova Tatijana G. ^3,4 , Shults Elvira E. ^1,4

Affiliations

1	(Данные Web of science) Novosibirsk Organ Chem Inst, Siberian Branch, Med Chem Lab, Novosibirsk, Russia
2	(Данные Web of science) Pepoples Friendship Univ Russia, 6 Miklukho Maklaya St, Moscow 117198, Russia
3	(Данные Web of science) Russian Acad Sci, Novosibirsk Organ Chem Inst, Siberian Branch, Lab Pharmacol Res, Novosibirsk, Russia
4	(Данные Web of science) Novosibirsk State Univ, Novosibirsk, Russia

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 beta,gamma-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.

Lipeeva A.V. , Baev D.S. , Dolgikh M.P. , Tolstikova T.G. , Shults E.E.
Rapid Access to Oxazine Fused Furocoumarins and in vivo and in silico Studies of theirs Biological Activity
Medicinal Chemistry. 2017. V.13. N7. P.625-632. DOI: 10.2174/1573406413666170601114527 WOS Scopus РИНЦ OpenAlex

Published print:

Oct 17, 2017

Web of science:	WOS:000414012200003
Scopus:	2-s2.0-85038129621
Elibrary:	35518519
OpenAlex:	W2621370364

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