Rapid access to oxazine fused furocoumarins and in vivo and in silico studies of theirs biological activity

Alla V. Lipeeva, Dmitry S. Baev, Margarita P. Dolgikh, Tatijana G. Tolstikova, Elvira E. Shults

    Research output: Contribution to journalArticlepeer-review

    3 Citations (Scopus)

    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 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.

    Original languageEnglish
    Pages (from-to)625-632
    Number of pages8
    JournalMedicinal Chemistry
    Volume13
    Issue number7
    DOIs
    Publication statusPublished - 2017

    Keywords

    • Analgesic activity
    • Anti-inflammatory activity
    • Furocoumarins
    • Gold catalysis
    • Molecular docking
    • Oximes
    • Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis
    • Catalytic Domain
    • Indomethacin/pharmacology
    • Furocoumarins/chemical synthesis
    • Oxazines/chemical synthesis
    • Cyclic Nucleotide Phosphodiesterases, Type 4/chemistry
    • Animals
    • Rolipram/pharmacology
    • Mice
    • Molecular Docking Simulation
    • Diclofenac/pharmacology
    • Drug Evaluation, Preclinical
    • Analgesics/chemical synthesis
    • gold catalysis
    • oximes
    • MEDICINAL CHEMISTRY
    • ISOXAZOLES
    • STREPTOMYCES
    • PLANT COUMARINS
    • DERIVATIVES
    • METABOLITES
    • GOLD CATALYSIS
    • anti-inflammatory activity
    • OXIMES
    • PEUCEDANIN
    • molecular docking
    • OREOSELONE
    • furocoumarins

    Fingerprint Dive into the research topics of 'Rapid access to oxazine fused furocoumarins and in vivo and in silico studies of theirs biological activity'. Together they form a unique fingerprint.

    Cite this