Novel Benzimidazole-Endowed Chalcones as α-Glucosidase and α-Amylase Inhibitors: An Insight into Structural and Computational Studies

In search of novel antidiabetic agents, we synthesized a new series of chalcones with benzimidazole scaffolds by an efficient ‘one-pot’ nitro reductive cyclization method and evaluated their α-glucosidase and α-amylase inhibition studies. The ‘one-pot’ nitro reductive cyclization method offered a si...

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Main Authors: Prashasthi V. Rai, Ramith Ramu, P. Akhileshwari, Sudharshan Prabhu, Nupura Manish Prabhune, P. V. Deepthi, P. T. Anjana, D. Ganavi, A. M. Vijesh, Khang Wen Goh, Mohammad Z. Ahmed, Vasantha Kumar
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/29/23/5599
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Summary:In search of novel antidiabetic agents, we synthesized a new series of chalcones with benzimidazole scaffolds by an efficient ‘one-pot’ nitro reductive cyclization method and evaluated their α-glucosidase and α-amylase inhibition studies. The ‘one-pot’ nitro reductive cyclization method offered a simple route for the preparation of benzimidazoles with excellent yield and higher purity compared to the other conventional acid- or base-catalyzed cyclization methods. <sup>1</sup>H, <sup>13</sup>C NMR, IR, and mass spectrum data were used to characterize the compounds. Single-crystal XRD data confirmed the 3D structure of compound <b>7c,</b> which was crystalized in the P<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mover accent="true"><mn>1</mn><mo>¯</mo></mover></semantics></math></inline-formula> space group of the triclinic crystal system. Hirshfeld surface analysis validates the presence of O-H..O, O-H…N, and C-H…O intermolecular hydrogen bonds. From the DFT calculations, the energy gap between the frontier molecular orbitals in <b>7c</b> was found to be 3.791 eV. From the series, compound <b>7l</b> emerged as a potent antidiabetic agent with IC<sub>50</sub> = 22.45 ± 0.36 µg/mL and 20.47 ± 0.60 µg/mL against α-glucosidase and α-amylase enzymes, respectively. The in silico molecular docking studies revealed that compound <b>7l</b> has strong binding interactions with α-glucosidase and α-amylase proteins. Molecular dynamics studies also revealed the stability of compound <b>7l</b> with α-glucosidase and α-amylase proteins.
ISSN:1420-3049