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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2024-11, Vol.29 (23), p.5599
• Main Authors: Rai, Prashasthi V, Ramu, Ramith, Akhileshwari, P, Prabhu, Sudharshan, Prabhune, Nupura Manish, Deepthi, P V, Anjana, P T, Ganavi, D, Vijesh, A M, Goh, Khang Wen, Ahmed, Mohammad Z, Kumar, Vasantha
• Format: Article
• Language: English
• Subjects: alpha-Amylases - antagonists & inhibitors; alpha-Amylases - chemistry; alpha-Glucosidases - chemistry; alpha-Glucosidases - metabolism; Amylases; Anticonvulsants; Antidiabetics; benzimidazoles; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Cancer; chalcones; Chalcones - chemistry; Chalcones - pharmacology; Comparative analysis; crystal structure; Crystallography, X-Ray; Diabetes; docking studies; Energy; Glycoside Hydrolase Inhibitors - chemical synthesis; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Hydrogen; Hydrogen Bonding; Hydrogen bonds; Hypoglycemic agents; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Insulin; Molecular Docking Simulation; Molecular dynamics; Molecular Structure; Pharmaceutical sciences; Proteins; Structure-Activity Relationship; Type 2 diabetes; α-amylase; α-glucosidase
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29235599

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. H, C NMR, IR, and mass spectrum data were used to characterize the compounds. Single-crystal XRD data confirmed the 3D structure of compound which was crystalized in the P1¯ 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 was found to be 3.791 eV. From the series, compound emerged as a potent antidiabetic agent with IC = 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 has strong binding interactions with α-glucosidase and α-amylase proteins. Molecular dynamics studies also revealed the stability of compound with α-glucosidase and α-amylase proteins.