Potential antidiabetic activity and molecular docking studies of novel synthesized 3.6-dimethyl-5-oxo-pyrido[3,4-f][1,2,4]triazepino[2,3-a]benzimidazole and 10-amino-2-methyl-4-oxo pyrimido[1,2-a]benzimidazole derivatives

Abstract

Diabetes affects a large population of the globe and is considered as a leading cause of death. Many synthetic and natural inhibitors have been developed for diabetes treatment. Herein, we report the potential antidiabetic activity of two new heterocyclic systems, namely 3.6-dimethyl-5-oxo-pyrido[3,4f][1,2,4]triazepino[2,3-a]benzimidazole (I) and 10-amino-2-methyl-4-oxo pyrimido[1,2-a]benzimidazole (II) against three related enzymes: α-amylase, α-glucosidase and β-galactosidase. Compounds I and II were synthesized by the action of DMF-DMA and dimethyl sulfate in the presence of water on 2-methyl-3H-benzimidazolo[1,2b][1,2,4]triazepin-4(5H)-one, and are characterized by single X-ray diffraction. The binding interaction modes in the active sites of I and II and targeted enzymes (stable complexes ligand-receptor) are emphasized using the molecular docking approach by applying the Lamarckian genetic algorithm method. Furthermore, plausible mechanisms have been proposed explaining their synthesis. Hirshfeld surface analysis reveals the nature of molecular interactions and fingerprint plots provide information about the percentage contribution from each individual molecular contact to the structure surface. Graphical abstract Left Molecular packing of 1,4-dimethyl-2-oxo-pyrimido[1,2-a]benzimidazole hydrate. Right Docking active site of α-glucosidase.

Synthesis, Crystal Structure and Computational Investigation of New 4‐Phenyl‐decahydro‐1H‐1,5‐benzodiazepin‐2‐one as Potent Inhibitor of Mu‐opioid Receptor

“…The Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) of the mu‐opioid receptor‐ 1 complex, which can give information on the interaction stability of 1 in the mu‐opioid receptor binding environment are shown in Figure . From Fig 9a, the RMSD plot indicates that the mu‐opioid receptor‐ 1 complex belongs to a large conformation due to the system convergence at above 3 Å.…”

“…In continuation of our studies on functionalized heterocycles and our previous works on 1,5‐benzodiazepine derivatives, we report the synthesis, crystal structure and Hirshfeld surface analysis of 4‐phenyl‐decahydro‐1H‐1,5‐benzodiazepin‐2‐one ( 1 ) obtained by hydrogenation of 4‐phenyl‐5a,6,7,8,9,9a‐hexahydro‐1H‐1,5‐benzodiazepin‐2(5H)‐one in the presence of palladium on activated charcoal in anhydrous ethanol. (Scheme ).…”

Potential antidiabetic activity of benzimidazole derivative albendazole and lansoprazole drugs in different doses in experimental type 2 diabetic rats

“…Some benzimidazoles have been reported to have antidiabetic effects by mainly activation of AMPK and PPAR, inhibition of α-amylase and α-glucosidase enzymes and other antidiabetic mechanisms. [10,[26][27][28]. However, these effects on AMPK may vary depending on the dose, the ratio of binding to the AMPK, and activating different subunits of AMPK [5].…”

“…In conclusion, new studies are carried out to show that different benzimidazole derivatives may have antidiabetic effects through AMPK, PPARγ, α-glucosidase, and other pathways. Structural compatibility of benzimidazoles on antidiabetic mechanisms is especially important [28,40,41]. The AMPK and PPARγ activation have been considered as alternative important targets for the treatment of T2D and obesity in recent years.…”

Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase

“…2, in order to ascertain the influence of the methyl group in 1 upon the molecular packing. Further, based on the wide biological interest of pyridazine derivatives, alluded to above, and due to our continuing interests on the synthesis of heterocyclic systems with remarkable anti-inflammatory and anti-diabetic activities [23][24][25], 1 was also evaluated for anti-inflammatory and enzyme inhibitory activities using an α-Glucosidase inhibition assay.…”