Dataset : Synthesis, antidiabetic activity and molecular docking study of rhodanine-substitued spirooxindole pyrrolidine derivatives as novel α-amylase inhibitors

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General metadata

Identifiers :
local : FR-18008901306731-2022-05-13 external : ccdc:1994835 , doi:10.1016/j.bioorg.2020.104507
Description :
In a sustained search for novel α-amylase inhibitors for the treatment of type 2 diabetes mellitus (T2DM), we report herein the synthesis of a series of nineteen novel rhodanine-fused spiro[pyrrolidine-2,3′-oxindoles]. They were obtained by one-pot three component [3 + 2] cycloaddition of stabilized azomethine ylides, generated in situ by condensation of glycine methyl ester and the cyclic ketones 1H-indole-2,3-dione (isatin), with (Z)-5-arylidine-2-thioxothiazolidin-4-ones. The highlight of this protocol is the efficient high-yield construction of structurally diverse rhodanine-fused spiro[pyrrolidine-2,3′-oxindoles] scaffolds, including four contiguous stereocenters, along with excellent regio- and diastereoselectivities. The stereochemistry of all compounds was confirmed by NMR and corroborated by an X-ray diffraction study performed on one derivative. All cycloadducts were evaluated in vitro for their α-amylase inhibitory activity and showed good α-amylase inhibition with IC50 values ranging between 1.49 ± 0.10 and 3.06 ± 0.17 µM, with respect to the control drug acarbose (IC50 = 1.56 µM). Structural activity relationships (SARs) were also established for all synthesized compounds and the binding interactions of the most active spiropyrrolidine derivatives were modelled by means of molecular in silico docking studies. The most potent compounds 5 g, 5 k, 5 s and 5 l were further screened in vivo for their hypoglycemic activity in alloxan-induced diabetic rats, showing a reduction of the blood glucose level. Therefore, these spiropyrrolidine derivatives may be considered as promising candidates for the development of new classes of antidiabetic drugs.
Disciplines :
chemistry, organic (chemistry), crystallography (chemistry), materials science, characterization & testing (chemistry), mathematical & computational biology (fundamental biology), microbiology (fundamental biology)
Keywords :

Dates :
Data acquisition : from 2017 to 2020
Data provision : 26 Nov 2020
Metadata record : Creation : 13 May 2022

Update periodicity : no update
Language : English (eng)
Audience : University: master, Research
RightsAttribution
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Collection

Quotation

Amani Toumi, Sarra Boudriga, Khaled Hamden, Mansour Sobeh, Mohammed Cheurfa, Mohedinne Askri, Michael Knorr, Carsten Strohmann, Lukas Brieger (2020): Synthesis, antidiabetic activity and molecular docking study of rhodanine-substitued spirooxindole pyrrolidine derivatives as novel α-amylase inhibitors. Elsevier. ccdc:1994835

Administrative metadata

Data creators : Amani Toumi [1], Sarra Boudriga [1], Khaled Hamden [2], Mansour Sobeh [3], Mohammed Cheurfa [3], Mohedinne Askri [1], Michael Knorr [4] [5], Carsten Strohmann [6], Lukas Brieger [6]
[1] : Département de Chimie, Faculté des Sciences de Monastir
[2] : Bioressources : Biologie Intégrative & Valorisation «BIOLIVAL » - Institut Supérieur de Biotechnologie de Monastir - LR14ES06
[3] : Mohammed VI Polytechnic University
[4] : Institut UTINAM (UMR 6213) (Université de Franche-Comté)
[5] : Observatoire des Sciences de l'Univers - Terre, Homme, Environnement, Temps, Astronomie (UAR 3245) (Université de Franche-Comté)
[6] : Technische Universität Dortmund
Publisher : Elsevier
Science contact : Michael Knorr website e-mail
Project and funders :
Access : available

Technical metadata

Formats : application/msword, application/pdf, chemical/x-cif
Data acquisition methods :
  • Experimental data :
    X-ray diffraction
    Organic synthesis
    Biological tests
    In-vitro and In-vivo tests
    Cycloaddition
    DFT (Density Functional Theory) calculations
    NMR spectroscopy
Datatype : Dataset

Publications

  • Synthesis, antidiabetic activity and molecular docking study of rhodanine-substitued spirooxindole pyrrolidine derivatives as novel α-amylase inhibitors (doi:10.1016/j.bioorg.2020.104507)
  • Antimicrobial Activity and In Silico Molecular Docking Studies of Pentacyclic Spiro[oxindole-2,3′-pyrrolidines] Tethered with Succinimide Scaffolds (doi:10.3390/app12010360)

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Université de Bourgogne, Université de Franche-Comté, UTBM, AgroSup Dijon, ENSMM, BSB, Arts des Metiers