Synthesis, biological evaluation and induced fit docking simulation study of<scp>d</scp>-glucose-conjugated 1H-1,2,3-triazoles having 4H-pyrano[2,3-d]pyrimidine ring as potential agents against bacteria and fungi

Hai, Son; Ha, Nguyen Thi Thu; Tung, Do Tien; Hương, Nguyêñ Thị Thu; Anh, Hoang Huu; Hoàng, Thi Kim Van; Vu, Ngoc Toan; Toan, Duong Ngoc; Thành, Nguyễn Đình

doi:10.1039/d1nj05330b

Cited by 8 publications

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“…N -heterocyclic compounds especially those with triazole rings such as 1,2,3-triazole have different biological properties such as anti-Alzheimer, , anti-viral, , anti-fungal, antibacterial and antitubercular, anti-cancer, anti-tubulin, − and anti-diabetes − activity. Till date, many scaffolds containing 1,2,3-triaole rings with significant inhibitory activity against α-glucosidase have been reported (some of them are depicted in Figure , compounds A , B , and C − ).…”

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confidence: 99%

Novel Pyrano[3,2-c]quinoline-1,2,3-triazole Hybrids as Potential Anti-Diabetic Agents: In Vitro α-Glucosidase Inhibition, Kinetic, and Molecular Dynamics Simulation

et al. 2023

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In this study, a novel series of pyrano[3,2-c]quinoline-1,2,3-triazole hybrids 8a−o were synthesized and evaluated against the α-glucosidase enzyme. All compounds showed significant in vitro inhibitory activity (IC 50 values of 1.19 ± 0.05 to 20.01 ± 0.02 μM) compared to the standard drug acarbose (IC 50 = 750.0 μM). Among them, 2-amino-4-(3-((1-benzyl-1H-1,2,3-triazol-4yl)methoxy)phenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile (compound 8k) demonstrated the best inhibitory effect toward α-glucosidase (IC 50 = 1.19 ± 0.05 μM) with a competitive pattern of inhibition. Since compound 8k was synthesized as a racemic mixture, molecular docking and dynamics simulations were performed on R-and S-enantiomers of compound 8k. Based on the molecular docking results, both R-and S-enantiomers of compound 8k displayed significant interactions with key residues including catalytic triad (Asp214, Glu276, and Asp349) in the enzyme active site. However, an in silico study indicated that S-and Renantiomers were inversely located in the enzyme active site. The R-enantiomer formed a more stable complex with a higher binding affinity to the active site of α-glucosidase than that of the S-enantiomer. The benzyl ring in the most stable complex ((R)-compound 8k) was located in the bottom of the binding site and interacted with the enzyme active site, while the pyrano[3,2-c]quinoline moiety occupied the high solvent accessible entrance of the active site. Thus, the synthesized pyrano[3,2-c]quinoline-1,2,3-triazole hybrids seem to be promising scaffolds for the development of novel α-glucosidase inhibitors.

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