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Letters in Organic Chemistry

Author(s): Vijayan R. Akhila, Maheswari R. Priya, Daisy R. Sherin, Girija K. Krishnapriya, Sreerekha V. Keerthi, Thanathu K. Manojkumar and Kallikat N. Rajasekharan*

DOI: 10.2174/1570178615666180815124425

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Mechanochemical Synthesis, in vitro Evaluation and Molecular Docking Studies of 4-Amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles as Antidiabetic Agents

Page: [560 - 568] Pages: 9

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Abstract

The synthesis of 4-amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles 4a-h, as example of 2,4-diaminothiazole-benzofuran hybrids and an evaluation of their antidiabetic activity, by in vitro and computational methods, are reported. The synthesis of these diaminothiazoles was achieved mechano chemically by a rapid solvent-less method. Their antidiabetic activity was assessed by α-glucosidase and α-amylase inhibition assays. The, IC50 value for α-glucosidase inhibition by 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) was found to be 20.04 µM and the IC50 value for α-amylase inhibition, 195.03 µM, whereas the corresponding values for reference acarbose were 53.38 µM and 502.03 µM, respectively. Molecular docking studies at the active sites of α- glucosidase and α-amylase showed that among the diaminothiazoles 4a-h now studied, 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) has the highest D-scores of -8.63 and -8.08 for α-glucosidase and for α-amylase, with binding energies -47.76 and -19.73 kcal/mol, respectively.

Keywords: Mechanochemical, 2, 4-diaminothiazoles, α-glucosidase, α-amylase, molecular docking, alkaloids.

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