Synthesis, α-glucosidase inhibitory activity and in silico study of tris-indole hybrid scaffold with oxadiazole ring: as potential leads for the management of type-II diabetes mellitus

Muhammad Taha, Fazal Rahim, Syahrul Imran, Nor Hadiani Ismail, Hayat Ullah, Manikandan Selvaraj, Muhammad Tariq Javid, Uzma Salar, Muhammad Ali, Khalid Mohammed Khan

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76 Citations (Scopus)

Abstract

Discovery of α-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of type-II diabetes mellitus and the other carbohydrate mediated disease. In continuation of our drug discovery research on potential antidiabetic agents, we synthesized novel tris-indole-oxadiazole hybrid analogs (1 −2 1), structurally characterized by various spectroscopic techniques such as 1H NMR, EI-MS, and 13C NMR. Elemental analysis was found in agreement with the calculated values. All compounds were evaluated for α-glucosidase inhibiting potential and showed potent inhibitory activity in the range of IC50 = 2.00 ± 0.01–292.40 ± 3.16 μM as compared to standard acarbose (IC50 = 895.09 ± 2.04 µM). The pharmacokinetic predictions of tris-indole series using descriptor properties showed that almost all compounds in this series indicate the drug aptness. Detailed binding mode analyses with docking simulation was also carried out which showed that the inhibitors can be stabilized by the formation of hydrogen bonds with catalytic residues and the establishment of hydrophobic contacts at the opposite side of the active site.

Original languageEnglish
Pages (from-to)30-40
Number of pages11
JournalBioorganic Chemistry
Volume74
DOIs
Publication statusPublished - Oct 2017
Externally publishedYes

Keywords

  • Docking studies, SAR
  • Oxadiazole
  • Synthesis
  • Tris-indole
  • Type-II diabetes mellitus
  • α-Glucosidase inhibitors

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