Synthesis and evaluation of camphor and cytisine-based cyanopyrrolidines as DPP-IV inhibitors for the treatment of type 2 diabetes mellitus

S. O. Kuranov, I. P. Tsypysheva, M. V. Khvostov, Liana F. Zainullina, S. S. Borisevich, Yu V. Vakhitova, O. A. Luzina, N. F. Salakhutdinov

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    In this study, bornyl- and cytisine-based cyanopyrrolidines as potent dipeptidyl peptidase-IV (DPP-IV) inhibitors were synthesised. The in vitro inhibiting activities of bornyl- and cytisine derivatives towards DPP-IV were evaluated. Bornyl-based cyanopyrrolidines were shown to have moderate inhibitory activity with regard to DPP-IV (1.27–15.78 µM). A docking study was performed to elucidate the structure-activity relationship of the obtained compounds. The in vivo hypoglycemic activities of the same compounds were evaluated with the oral glucose tolerance test (OGTT) in mice. Bornyl-based cyanopyrrolidines were shown to have good hypoglycemic activity.

    Original languageEnglish
    Pages (from-to)4402-4409
    Number of pages8
    JournalBioorganic and Medicinal Chemistry
    Volume26
    Issue number15
    DOIs
    Publication statusPublished - 15 Aug 2018

    Keywords

    • DIPEPTIDYL-PEPTIDASE-IV
    • COMPLICATIONS
    • EPIDEMIOLOGY
    • DERIVATIVES
    • INSULIN
    • DESIGN
    • POTENT
    • DRUGS
    • Alkaloids/chemistry
    • Dipeptidyl-Peptidase IV Inhibitors/chemical synthesis
    • Humans
    • Male
    • Structure-Activity Relationship
    • Camphor/chemistry
    • Pyrrolidines/chemistry
    • Binding Sites
    • Catalytic Domain
    • Glucose Tolerance Test
    • Dipeptidyl Peptidase 4/chemistry
    • Hypoglycemic Agents/chemical synthesis
    • Quinolizines/chemistry
    • Animals
    • Diabetes Mellitus, Type 2/drug therapy
    • Mice
    • Molecular Docking Simulation
    • Azocines/chemistry

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