Synthesis of alpha amylase inhibitors based on privileged indole scaffold

Noreen T 1 , Taha M 2 , Imran S 3 , Chigurupati S 4 , Rahim F 5 , Selvaraj M 6 Show all authors , Ismail NH 3 , Mohammad JI 7 , Ullah H 5 , Javid MT 5 , Nawaz F 8 , Irshad M 1 , Ali M 9

Affiliations 

  • 1 Department of Chemistry, University of Wah, Quaid Avenue, Wah Cantt 47000, Pakistan; Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia
  • 2 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, UiTM Shah Alam, 40450 Shah Alam, Selangor D.E., Malaysia. Electronic address: taha_hej@yahoo.com
  • 3 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, UiTM Shah Alam, 40450 Shah Alam, Selangor D.E., Malaysia
  • 4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia
  • 5 Depatment of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, Pakistan
  • 6 Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia
  • 7 Department of Pharmacology, Faculty of Medicine, Cyberjaya University College of Medical Sciences, CUCMS, Cyberjaya 63000, Malaysia
  • 8 Department of Chemistry, University of Wah, Quaid Avenue, Wah Cantt 47000, Pakistan
  • 9 Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan
Bioorg Chem, 2017 06;72:248-255.
PMID: 28482265 DOI: 10.1016/j.bioorg.2017.04.010

Abstract

Twenty five derivatives of indole carbohydrazide (1-25) had been synthesized. These compounds were characterized using 1H NMR and EI-MS, and further evaluated for their α-amylase inhibitory potential. The analogs (1-25) showed varying degree of α-amylase inhibitory potential. ranging between 9.28 and 599.0µM when compared with standard acarbose having IC50 value 8.78±0.16µM. Six analogs, 25 (IC50=9.28±0.153µM), 22 (IC50=9.79±0.43µM), 4 (IC50=11.08±0.357µM), 1 (IC50=12.65±0.169µM), 8 (IC50=21.37±0.07µM) and 14 (IC50=43.21±0.14µM) showed potent α-amylase inhibition as compared to the standard acarbose (IC50=8.78±0.16µM). All other analogs displayed good to moderate inhibitory potential. Structure-activity relationship was established through the interaction of the active compounds with enzyme active site with the help of docking studies.

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

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