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Pyrano[3,2-c]quinoline Derivatives as New Class of

[ Vol. 15 , Issue. 1 ]

Author(s):

Zahra Heydari, Maryam Mohammadi-Khanaposhtani, Somaye Imanparast, Mohammad Ali Faramarzi, Mohammad Mahdavi *, Parviz R. Ranjbar* and Bagher Larijani   Pages 8 - 16 ( 9 )

Abstract:


Background: Pyrano[3,2-c]quinoline derivatives 6a–n were synthesized via simple two-step reactions and evaluated for their in vitro α-glucosidase inhibitory activity.

Methods: Pyrano[3,2-c]quinoline derivatives 6a–n derivatives were prepared from a two-step reaction: cycloaddition reaction between 1-naphthyl amine 1 and malonic acid 2 to obtain benzo[h]quinoline-2(1H)-one 3 and reaction of 3 with aryl aldehydes 4 and Meldrum’s acid 5. The anti- α-glucosidase activity and kinetic study of the synthesized compounds were evaluated using α-glucosidase from Saccharomyces cerevisiae and p-nitrophenyl-a-D-glucopyranoside as substrate. The α-glucosidase inhibitory activity of acarbose was evaluated as positive control.

Results: All of the synthesized compounds, except compounds 6i and 6n, showed more inhibitory activity than the standard drug acarbose and were also found to be non-cytotoxic. Among the synthesized compounds, 1-(2-bromophenyl)-1H-benzo[h]pyrano[3,2-c]quinoline-3,12(2H,11H)-dione 6e displayed the highest α-glucosidase inhibitory activity (IC50 = 63.7 ± 0.5 μM). Kinetic study of enzyme inhibition indicated that the most potent compound, 6e, is a non-competitive inhibitor of α-glucosidase with a Ki value of 72 μM. Additionally, based on the Lipinski rule of 5, the synthesized compounds were found to be potential orally active drugs.

Conclusion: Our results suggest that the synthesized compounds are promising candidates for treating type 2 diabetes.

Keywords:

α-Glucosidase, Type 2 diabetes, Kinetic study, Pyrano[3, 2-c]quinoline, Coumarin, Xanthones.α-Glucosidase, Type 2 diabetes, Kinetic study, Pyrano[3, 2-c]quinoline, Coumarin, Xanthones.

Affiliation:

School of Chemistry, College of Science, University of Tehran, Tehran, Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Department Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Department Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, School of Chemistry, College of Science, University of Tehran, Tehran, Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran



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