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

Kawde AN 1 , Taha M 2 , Alansari RS 3 , Almandil NB 4 , Anouar EH 5 , Uddin N 6 Show all authors , Rahim F 7 , Chigurupati S 8 , Nawaz M 9 , Hayat S 7 , Ibrahim M 4 , Elakurthy PK 10 , Vijayan V 11 , Morsy M 12 , Ibrahim H 13 , Baig N 12 , Khan KM 14

Affiliations 

  • 1 Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia. Electronic address: akawde@kfupm.edu.sa
  • 2 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. Electronic address: mtaha@iau.edu.sa
  • 3 College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
  • 4 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
  • 5 Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
  • 6 Department of Chemistry, University of Karachi, Karachi 75270, Pakistan
  • 7 Department of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, Pakistan
  • 8 Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia
  • 9 Department of Nano-Medicine Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
  • 10 Department of Formulation R&D, Alembic Pharmaceuticals Ltd., Vadodara, India
  • 11 Faculty of Pharmacy, Aimst University, 08100, Malaysia
  • 12 Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia
  • 13 Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt
  • 14 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Int J Biol Macromol, 2020 Jul 01;154:217-232.
PMID: 32173438 DOI: 10.1016/j.ijbiomac.2020.03.090

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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