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Medicinal Chemistry Research

, Volume 26, Issue 5, pp 916–928 | Cite as

Synthesis of 2-phenyl-1H-imidazo[4,5-b]pyridine as type 2 diabetes inhibitors and molecular docking studies

  • Muhammad TahaEmail author
  • Nor Hadiani Ismail
  • Syahrul Imran
  • Izzatul Ainaa
  • Manikandan Selvaraj
  • Mohd syukri baharudin
  • Muhammad Ali
  • Khalid Mohammed Khan
  • Nizam Uddin
Original Research

Abstract

A series of imidazo[4,5-b]pyridines (332) was synthesized and evaluated for their ability to inhibit Baker’s yeast α-glucosidase enzyme. The IC50 values for all compounds were in the range of 13.5–93.7 µM with compound 15, a 2,4-dihydroxy-substituted analog, displayed the most potent activity potential. Structure–activity relationship strongly suggested the presence of hydroxyl group at aromatic side chain as the main contributing factor towards the inhibitory potential. Findings also suggested that compounds having hydroxyl groups at ortho and para positions are able to inhibit α-glucosidase enzyme efficiently. This experimental observation was further supported by docking studies carried out on human intestinal maltase-glucoamylase enzyme (PDB ID: 3TOP). The –NH– group of imidazo-pyridine of compound 15 formed H-bond with Asp1526, while both hydroxyls of catechol formed H-bond with Asp1279. Imidazo-pyridine ring was well stabilized by ππ stacking with Phe1560, and other hydrophobic interactions involving side chain of Pro1159, Tyr1167, Asp1157, Met1421, Trp1369, Pro1318, and Lys1460. The catechol ring also forms several hydrophobic interactions with Phe1560, Trp1523, Trp1418, His1584, Try1251, Ile1218 and Trp1355.

Keywords

Imidazo[4,5-b]pyridine Type-2 Diabetes Pharmacokinetic prediction Molecular docking 

Notes

Acknowledgements

Dr. Muhammad Taha would like to acknowledge the Ministry of Higher Education for financial support under the Fundamental Research Grant Scheme (FRGS) with sponsorship reference numbers FRGS/1/2016/STG01/UiTM/02/2 and Universiti Teknologi MARA for the financial support under LESTARI grant 600-RMI/DANA /5/3/ lestari (54/2013). The author (Dr. M.A.) is also grateful to HEC Pakistan for providing a research grant vide 20-1933/NRPU/R&D/HEC/12/5017.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Supplementary material

44_2017_1806_MOESM1_ESM.pdf (2.9 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Muhammad Taha
    • 1
    • 2
    Email author
  • Nor Hadiani Ismail
    • 1
    • 2
  • Syahrul Imran
    • 1
    • 2
  • Izzatul Ainaa
    • 2
  • Manikandan Selvaraj
    • 3
    • 4
  • Mohd syukri baharudin
    • 1
    • 2
  • Muhammad Ali
    • 5
  • Khalid Mohammed Khan
    • 6
  • Nizam Uddin
    • 7
  1. 1.Atta-ur-Rahman Institute for Natural Product DiscoveryUniversiti Teknologi MARA (UiTM), Puncak Alam CampusBandar Puncak AlamMalaysia
  2. 2.Faculty of Applied Science Universiti Teknologi MARA (UiTM)Shah AlamMalaysia
  3. 3.Integrative Pharmacogenomics Institute (iPROMISE)Universiti Teknologi MARA (UiTM), Puncak Alam CampusBandar Puncak AlamMalaysia
  4. 4.Faculty of PharmacyUniversiti Teknologi MARA (UiTM), Puncak Alam CampusBandar Puncak AlamMalaysia
  5. 5.Department of ChemistryCOMSATS Institute of Information TechnologyAbbottabadPakistan
  6. 6.H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan
  7. 7.Batterje Medical College for Science & TechnologyJeddahKingdom of Saudi Arabia

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