Rapid access to oxazine fused furocoumarins and in vivo and in silico studies of theirs biological activity. / Lipeeva, Alla V.; Baev, Dmitry S.; Dolgikh, Margarita P. et al.
In: Medicinal Chemistry, Vol. 13, No. 7, 2017, p. 625-632.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Rapid access to oxazine fused furocoumarins and in vivo and in silico studies of theirs biological activity
AU - Lipeeva, Alla V.
AU - Baev, Dmitry S.
AU - Dolgikh, Margarita P.
AU - Tolstikova, Tatijana G.
AU - Shults, Elvira E.
N1 - Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
PY - 2017
Y1 - 2017
N2 - 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 ß,?-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.
AB - 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 ß,?-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.
KW - Analgesic activity
KW - Anti-inflammatory activity
KW - Furocoumarins
KW - Gold catalysis
KW - Molecular docking
KW - Oximes
KW - Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis
KW - Catalytic Domain
KW - Indomethacin/pharmacology
KW - Furocoumarins/chemical synthesis
KW - Oxazines/chemical synthesis
KW - Cyclic Nucleotide Phosphodiesterases, Type 4/chemistry
KW - Animals
KW - Rolipram/pharmacology
KW - Mice
KW - Molecular Docking Simulation
KW - Diclofenac/pharmacology
KW - Drug Evaluation, Preclinical
KW - Analgesics/chemical synthesis
KW - gold catalysis
KW - oximes
KW - MEDICINAL CHEMISTRY
KW - ISOXAZOLES
KW - STREPTOMYCES
KW - PLANT COUMARINS
KW - DERIVATIVES
KW - METABOLITES
KW - GOLD CATALYSIS
KW - anti-inflammatory activity
KW - OXIMES
KW - PEUCEDANIN
KW - molecular docking
KW - OREOSELONE
KW - furocoumarins
UR - http://www.scopus.com/inward/record.url?scp=85038129621&partnerID=8YFLogxK
U2 - 10.2174/1573406413666170601114527
DO - 10.2174/1573406413666170601114527
M3 - Article
C2 - 28571532
AN - SCOPUS:85038129621
VL - 13
SP - 625
EP - 632
JO - Medicinal Chemistry
JF - Medicinal Chemistry
SN - 1573-4064
IS - 7
ER -
ID: 9671272