3-Benzyl(phenethyl)-2-thioxobenzo[g]quinazolines as a new class of potent α-glucosidase inhibitors: synthesis and molecular docking study

Rashad Al-Salahi; Rohaya Ahmad; ElHassane Anouar; Nor Izzati Iwana Nor Azman; Mohamed Marzouk; Hatem A Abuelizz

doi:10.4155/fmc-2018-0141

3-Benzyl(phenethyl)-2-thioxobenzo[g]quinazolines as a new class of potent α-glucosidase inhibitors: synthesis and molecular docking study

Future Med Chem. 2018 Aug 1;10(16):1889-1905. doi: 10.4155/fmc-2018-0141. Epub 2018 Jun 8.

Authors

Rashad Al-Salahi¹, Rohaya Ahmad², ElHassane Anouar³, Nor Izzati Iwana Nor Azman², Mohamed Marzouk^{3

4}, Hatem A Abuelizz¹

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO box 2457, Riyadh 11451, Saudi Arabia.
² Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 shah Alam, Selangor Darul Ehsan, Malaysia.
³ Department of Chemistry, College of Science & Humanities, Prince Sattam bin Abdulaziz University, PO Box 83, Al Kharj 11942, Saudi Arabia.
⁴ Chemistry of Natural Products Group, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo 12622, Egypt.

PMID: 29882426
DOI: 10.4155/fmc-2018-0141

Abstract

Aim: Using a simple modification on a previously reported synthetic route, 3-benzyl(phenethyl)-2-thioxobenzo[g]quinazolin-4(3H)-ones (1 and 2) were synthesized with high yields. Further transformation of 1 and 2 produced derivatives 3-26, which were structurally characterized based on NMR and MS data, and their in vitro α-glucosidase inhibitory activity was evaluated using Baker's yeast α-glucosidase enzyme.

Results: Compounds 2, 4, 8, 12 and 20 exhibited the highest activity (IC₅₀ = 69.20, 59.60, 49.40, 50.20 and 83.20 μM, respectively) compared with the standard acarbose (IC₅₀ = 143.54 μM).

Conclusion: A new class of potent α-glucosidase inhibitors was identified, and the molecular docking predicted plausible binding interaction of the targets in the binding pocket of α-glucosidase and rationalized the structure-activity relationship (SARs) of the target compounds.

Keywords: antidiabetic; benzoquinazoline; molecular docking; α-glucosidase.

Publication types

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

MeSH terms

Glycoside Hydrolase Inhibitors / chemical synthesis*
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Molecular Docking Simulation*
Molecular Structure
Structure-Activity Relationship
alpha-Glucosidases / metabolism*

Substances

Glycoside Hydrolase Inhibitors
alpha-Glucosidases