Discovery of novel pyrido-pyrrolidine hybrid compounds as alpha-glucosidase inhibitors and alternative agent for control of type 1 diabetes

Interactions between Phenols and Alkylamides of Sichuan Pepper (Zanthoxylum Genus) in α-Glucosidase Inhibition: A Structural Mechanism Analysis

“…According to the inhibitory type determined by kinetic analysis, noncompetitive inhibitors (α-SOH and Que) should bind to the noncatalytic sites of α-Glu, whereas competitive or uncompetitive inhibitors (Rut, Hyp, and Myr-3-G) are proposed to compete with the substrate for catalytic-site amino acids residues, namely Asp214, Gln276, and Asp349 (Figure 8A). 57,58 In this study, it was demonstrated that three hydrogen bonds were formed between α-SOH and Asn241, His279, and Glu304, respectively, along with the optimum binding energy of −6.00 kcal/mol (Table 8, Figure 8B), while four hydrogen bonds were formed between Que and Glu304, Gly306, and Gln322, respectively, with the optimum binding energy of −7.35 kcal/ mol. In addition, Que was shown to interact with Glu304 and Thr307 by van der Waals force (Figure 8C).…”

“…According to the inhibitory type determined by kinetic analysis, noncompetitive inhibitors (α-SOH and Que) should bind to the noncatalytic sites of α-Glu, whereas competitive or uncompetitive inhibitors (Rut, Hyp, and Myr-3-G) are proposed to compete with the substrate for catalytic-site amino acids residues, namely Asp214, Gln276, and Asp349 (Figure A). , …”

Pyrrolidine Derivatives as Anti‐diabetic Agents: Current Status and Future Prospects

“…In general, all the synthesized derivatives were found to be highly potent (IC 50 Luthra et al have reported the synthesis of Pyrido-pyrrolidine hybrids as α-glucosidase inhibitors. [65] Synthetic steps involved the synthesis of 2-pyridone 153 from ethyl-2-ethoxyacetate 152 followed by hydrolysis of cyano group and cyclization to give (154). Further reaction of 154 and 156 under basic conditions led to the synthesis of targeted Pyridopyrrolidine hybrids 157 (Scheme 22).…”

Washingtonia filifera seed extracts inhibit the islet amyloid polypeptide fibrils formations and α-amylase and α-glucosidase activity

“…The three-dimensional (3 D) structure of IAPP 29 (PDB id: 2L86) and a-amylase 30 (PDB id: 1DHK) were obtained from protein data bank. However, due to the unavailability of the experimental 3 D structure of an a-glucosidase protein from Saccharomyces cerevisiae, we performed a template-based homology modelling using Swiss-model web server 31 with 3 D reference structure of isomaltase from Saccharomyces cerevisiae 32 (PDB id: 3AJ7) having 72% sequence identity 33 with the target protein structure. The predicted protein tertiary structure model was evaluated by local quality estimates 34 and Ramachandran plot of the dihedrals.…”