New benzimidazole‐oxadiazole derivatives: Synthesis, α‐glucosidase, α‐amylase activity, and molecular modeling studies as potential antidiabetic agents

Abstract

Benzimidazole‐1,3,4‐oxadiazole derivatives (5a–z) were synthesized and characterized with different spectroscopic techniques such as 1H NMR, 13C NMR, and HRMS. The synthesized analogs were examined against α‐glucosidase and α‐amylase enzymes to determine their antidiabetic potential. Compounds 5g and 5q showed the most activity with 35.04 ± 1.28 and 47.60 ± 2.16 µg/mL when compared with the reference drug acarbose (IC50 = 54.63 ± 1.95 µg/mL). Compounds 5g, 5o, 5s, and 5x were screened against the α‐amylase enzyme and were found to show excellent potential, with IC50 values ranging from 22.39 ± 1.40 to 32.07 ± 1.55 µg/mL, when compared with the standard acarbose (IC50 = 46.21 ± 1.49 µg/mL). The antioxidant activities of the effective compounds (5o, 5g, 5s, 5x, and 5q) were evaluated by TAS methods. A molecular docking research study was conducted to identify the active site and explain the functions of the active chemicals. To investigate the most likely binding mode of the substances 5g, 5o, 5q, 5s, and 5x, a molecular dynamics simulation was also carried out.

Synthesis, Anticancer Activity, and In Silico Modeling of Alkylsulfonyl Benzimidazole Derivatives: Unveiling Potent Bcl-2 Inhibitors for Breast Cancer

“…The profiles remained predominantly below the 0.6 nm mark; a threshold often associated with stable ligand–protein interactions. In the context of protein flexibility, Figure b illustrates the root-mean-square fluctuation (RMSF) for the Bcl-2 backbone . This plot is instrumental in deciphering the flexibility across the protein sequence upon ligand binding.…”

“…In the context of protein flexibility, Figure 3b illustrates the root-mean-square fluctuation (RMSF) for the Bcl-2 backbone. 55 This plot is instrumental in deciphering the flexibility across the protein sequence upon ligand binding. Certain residues are highlighted by pronounced peaks in the RMSF values, suggesting regions of increased mobility which may be critical for the protein's functional dynamics or for accommodating the ligand.…”

Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives

“…Therefore, the inhibition of α-glucosidase activity can delay carbohydrate ingestion and reduce postprandial hyperglycemia [ 10 ]. Up to now, increasingly more α-glucosidase inhibitors have been developed, but only a few inhibitors are clinically used for the treatment of type 2 diabetes, such as acarbose, voglibose, and miglitol [ 11 , 12 , 13 ]. Moreover, long-term use of these drugs also leads to some gastrointestinal side effects, including diarrhea and flatulence [ 14 , 15 ].…”

“…In order to find indolo [1,2-b]isoquinolines with potential pharmaceutical activity, we developed an efficient synthesis strategy and obtained a series of derivatives (1-20) [25]. In consideration of these, we evaluated the anti-α-glucosidase activity of indolo [1,2-b]isoquinoline derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), conducted SAR analysis, revealed the inhibition mechanism, and analyzed the drug-like properties and cytotoxicity.…”

Crystal Structure, DFT Calculation, and Hirshfeld Surface Analysis of the 1-(Cyclohex-1-en-1-yl)-3-(prop-2-yn-1-yl)-1,3-dihydro-2H-benzimidazol-2-one

“…Benzimidazoles containing nitrogen are well known for their wide range of biological activities [1][2][3][4]. In addition, they have been studied extensively for their anticancer activity [5], antifungal agents [1,6], antiviral activity [7,8], and antidiabetic properties [9,10]. Moreover, the benzimidazolone nucleus is often used as a scaffold for the development of therapeutic molecules with medicinal and biological applications.…”