Synthesis of quinoline derivatives as diabetic II inhibitors and molecular docking studies

Muhammad Taha; Sadia Sultan; Syahrul Imran; Fazal Rahim; Khalid Zaman; Abdul Wadood; Ashfaq Ur Rehman; Nizam Uddin; Khalid Mohammed Khan

doi:10.1016/j.bmc.2019.07.035

Synthesis of quinoline derivatives as diabetic II inhibitors and molecular docking studies

Bioorg Med Chem. 2019 Sep 15;27(18):4081-4088. doi: 10.1016/j.bmc.2019.07.035. Epub 2019 Jul 20.

Authors

Muhammad Taha¹, Sadia Sultan², Syahrul Imran³, Fazal Rahim⁴, Khalid Zaman⁴, Abdul Wadood⁵, Ashfaq Ur Rehman⁵, Nizam Uddin⁶, Khalid Mohammed Khan⁷

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: [email protected].
² Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia.
³ Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia.
⁴ Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
⁵ Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
⁶ Department of Chemistry, University of Karachi, Karachi 75270, Pakistan.
⁷ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.

PMID: 31378594
DOI: 10.1016/j.bmc.2019.07.035

Abstract

In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1-25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC₅₀ = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC₅₀values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC₅₀ = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC₅₀ = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like ¹H NMR, ¹³C NMR and ESIMS were used for characterization.

Keywords: Diabetic II; Molecular docking; Quinoline derivatives; Synthesis; α-Glucosidase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus / drug therapy*
Humans
Molecular Docking Simulation / methods*
Quinolines / chemical synthesis*
Structure-Activity Relationship

Substances

Quinolines