Synthesis of indole derivatives as diabetics II inhibitors and enzymatic kinetics study of α-glucosidase and α-amylase along with their in-silico study

Taha M 1 , Alrashedy AS 2 , Almandil NB 3 , Iqbal N 4 , Anouar EH 5 , Nawaz M 6 Show all authors , Uddin N 7 , Chigurupati S 8 , Wadood A 9 , Rahim F 10 , Das S 11 , Venugopal V 12 , Nawaz F 13 , Khan KM 14

Affiliations 

  • 1 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
  • 2 College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
  • 3 Department of clinical pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
  • 4 Department of Chemistry, University of Poonch, Rawalakot, AJK, Pakistan
  • 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 Nano-Medicine Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
  • 7 Department of Chemistry, University of Karachi, Karachi 75270, Pakistan
  • 8 Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah, 52571, Saudi Arabia
  • 9 Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
  • 10 Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
  • 11 Department of Pharmacology, Faculty of Medicine, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia
  • 12 School of Pharmacy, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry 607402, India
  • 13 Department of Chemistry, University of Wah, Quaid Avenue, Wah Cantt 47000, Pakistan
  • 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, 2021 Nov 01;190:301-318.
PMID: 34481854 DOI: 10.1016/j.ijbiomac.2021.08.207

Abstract

In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC50 = 3.80 to 47.50 μM), and α-glucosidase inhibitory interactions (IC50 = 3.10-52.20 μM) in comparison with standard acarbose (IC50 = 12.28 μM and 11.29 μM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase.

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

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