Synthesis, α-amylase inhibitory potential and molecular docking study of indole derivatives

Muhammad Taha; Mohd Syukri Baharudin; Nor Hadiani Ismail; Syahrul Imran; Muhammad Naseem Khan; Fazal Rahim; Manikandan Selvaraj; Sridevi Chigurupati; Muhammad Nawaz; Faiza Qureshi; Shantini Vijayabalan

doi:10.1016/j.bioorg.2018.05.021

Synthesis, α-amylase inhibitory potential and molecular docking study of indole derivatives

Bioorg Chem. 2018 Oct:80:36-42. doi: 10.1016/j.bioorg.2018.05.021. Epub 2018 May 22.

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 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, Universiti Teknologi MARA, 40450 Shah Alam, Selangor D. E, Malaysia.
³ Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan.
⁴ Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
⁵ Monash University School of Chemical Engineering, Bandar Subway 47500, Selangor, Malaysia.
⁶ Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah 51452, Saudi Arabia.
⁷ 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.
⁸ Deanship of Scientific Research, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; 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.
⁹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, Bedong 08100, Malaysia.

PMID: 29864686
DOI: 10.1016/j.bioorg.2018.05.021

Abstract

In search of potent α-amylase inhibitor we have synthesized eighteen indole analogs (1-18), characterized by NMR and HR-EIMS and screened for α-amylase inhibitory activity. All analogs exhibited a variable degree of α-amylase inhibition with IC₅₀ values ranging between 2.031 ± 0.11 and 2.633 ± 0.05 μM when compared with standard acarbose having IC₅₀ values 1.927 ± 0.17 μM. All compounds showed good α-amylase inhibition. Compound 14 was found to be the most potent analog among the series. Structure-activity relationship has been established for all compounds mainly based on bringing about the difference of substituents on phenyl ring. To understand the binding interaction of the most active analogs molecular docking study was performed.

Keywords: Docking studies; Indole; SAR. Thiourea; Synthesis; α-amylase.

Publication types

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

MeSH terms

Binding Sites
Catalytic Domain
Glycoside Hydrolase Inhibitors / chemical synthesis*
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / metabolism
Indoles / chemical synthesis
Indoles / chemistry*
Indoles / metabolism
Inhibitory Concentration 50
Molecular Docking Simulation
Structure-Activity Relationship
alpha-Amylases / antagonists & inhibitors
alpha-Amylases / metabolism*

Substances

Glycoside Hydrolase Inhibitors
Indoles
alpha-Amylases