Isatin thiazoles as antidiabetic: Synthesis, in vitro enzyme inhibitory activities, kinetics, and in silico studies.

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  • Additional Information
    • Source:
      Publisher: Wiley-VCH Verlag GmbH & Co. KGaA Country of Publication: Germany NLM ID: 0330167 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-4184 (Electronic) Linking ISSN: 03656233 NLM ISO Abbreviation: Arch Pharm (Weinheim) Subsets: MEDLINE
    • Publication Information:
      Publication: <2005->: Weinheim Germany : Wiley-VCH Verlag GmbH & Co. KGaA
      Original Publication: Weinheim, Verlag Chemie GmbH.
    • Subject Terms:
      Hypoglycemic Agents*/chemical synthesis ; Hypoglycemic Agents*/pharmacology ; Isatin*/chemical synthesis ; Isatin*/pharmacology ; Thiazoles*/chemical synthesis ; Thiazoles*/pharmacology; Diabetes Mellitus ; Glycoside Hydrolase Inhibitors/chemical synthesis ; Glycoside Hydrolase Inhibitors/pharmacology ; Humans ; Kinetics ; Molecular Docking Simulation ; Molecular Structure ; Structure-Activity Relationship ; alpha-Amylases/antagonists & inhibitors ; alpha-Glucosidases/metabolism
    • Abstract:
      Diabetes mellitus is one of the most prevalent diseases nowadays. Several marketed drugs are available for the cure and treatment of diabetes, but there is still a dire need of introducing compatible drug molecules with lesser side effects. The current study is based on the synthesis of isatin thiazole derivatives 4-30 via the Hantzsch reaction. The synthetic compounds were characterized using different spectroscopic techniques and evaluated for their α-amylase and α-glucosidase inhibition potential. Of 27 isatin thiazoles, five (4, 5, 10, 12, and 16) displayed good activities against the α-amylase enzyme with IC 50 values in the range of 22.22 ± 0.02-27.01 ± 0.06 µM, and for α-glucosidase, the IC 50 values of these compounds were in the range of 20.76 ± 0.17-27.76 ± 0.17 µM, respectively. The binding interactions of the active molecules within the active site of enzymes were studied with the help of molecular docking studies. In addition, kinetic studies were carried out to examine the mechanism of action of the synthetic molecules as well. Compounds 3a, 4, 5, 10, 12, and 16 were also examined for their cytotoxic effect and were found to be noncytotoxic. Thus, several molecules were identified as good antihyperglycemic agents, which can be further modified to enhance inhibition ability and to find the lead molecule that can act as a potential antidiabetic agent.
      (© 2022 Deutsche Pharmazeutische Gesellschaft.)
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    • Grant Information:
      SHEC/SRSP/Med-3/15/2021-21 Sindh Higher Education Commission (SHEC), Pakistan
    • Contributed Indexing:
      Keywords: Hantzsch thiazole synthesis; antidiabetic activity; isatin thiazole; kinetic studies; molecular docking
    • Accession Number:
      0 (Glycoside Hydrolase Inhibitors)
      0 (Hypoglycemic Agents)
      0 (Thiazoles)
      82X95S7M06 (Isatin)
      EC 3.2.1.1 (alpha-Amylases)
      EC 3.2.1.20 (alpha-Glucosidases)
    • Publication Date:
      Date Created: 20220331 Date Completed: 20220602 Latest Revision: 20220608
    • Publication Date:
      20240104
    • Accession Number:
      10.1002/ardp.202100481
    • Accession Number:
      35355329