Exploring efficacy of indole-based dual inhibitors for α-glucosidase and α-amylase enzymes: In silico, biochemical and kinetic studies

Abdel Nasser Kawde*, Muhammad Taha, Raneem Saud Alansari, Noor Barak Almandil, El Hassane Anouar, Nizam Uddin, Fazal Rahim, Sridevi Chigurupati, Muhammad Nawaz, Shawkat Hayat, Mohamad Ibrahim, Praveen Kumar Elakurthy, Venugopal Vijayan, Mohamed Morsy, Hossieny Ibrahim, Nadeem Baig, Khalid Mohammed Khan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

α-Glucosidase and α-amylase are enzymes which are associated with diabetic II. These enzymes break macromolecules of sugar into monosugar molecules which is soluble in body, hence increase the sugar level in blood. There is need to develop economical and save inhibitors to prevent them from breaking sugar macromolecules to soluble molecules which will control the level of sugar in blood. Therefore, we synthesized indole-based derivatives (1–18) and evaluated as dual inhibitor for α-glucosidase and α-amylase. These chemical scaffolds were built with variation in aryl ring which were found active with good to moderate activity for α-glucosidase having IC50 value ranging from 13.99 ± 0.10 to 59.09 ± 0.30 μM when compared with standard acarbose with IC50 of 11.29 ± 0.10 μM; for α-amylase IC50 value ranging from 13.14 ± 0.10 to 58.99 ± 0.30 μM when compared with the standard acarbose with IC50 of 11.12 ± 0.10 μM. Structure activity relationship (SAR) has been established for all compounds. Enzymatic kinetic study and molecular docking study have been carried out to investigate the binding interactions α-glucosidase and α-amylase enzyme.

Original languageEnglish
Pages (from-to)217-232
Number of pages16
JournalInternational Journal of Biological Macromolecules
Volume154
DOIs
StatePublished - 1 Jul 2020

Bibliographical note

Publisher Copyright:
© 2020

Keywords

  • Enzymatic kinetic study
  • Indole
  • Molecular docking
  • α-Amylase
  • α-Glucosidase

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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