Molecular Docking, Kinetics Study, and Structure–Activity Relationship Analysis of Quercetin and Its Analogous as Helicobacter pylori Urease Inhibitors

2012 ◽  
Vol 60 (42) ◽  
pp. 10572-10577 ◽  
Author(s):  
Zhu-Ping Xiao ◽  
Xu-Dong Wang ◽  
Zhi-Yun Peng ◽  
Shen Huang ◽  
Pan Yang ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Molecular Docking ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Urease Inhibitors ◽  
Kinetics Study ◽  
Relationship Analysis ◽  
Structure Activity

Structure-Activity Relationship of Omeprazole and Analogs as Helicobacter pylori Urease Inhibitors

1995 ◽  
Vol 38 (25) ◽  
pp. 4906-4916 ◽  
Author(s):  
Thomas C. Kuehler ◽  
Jan Fryklund ◽  
Nils-ke Bergman ◽  
Jessica Weilitz ◽  
Adrian Lee ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Urease Inhibitors ◽  
Structure Activity ◽  
Relationship Of

scholarly journals Trifluoromethylated Flavonoid-Based Isoxazoles as Antidiabetic and Anti-Obesity Agents: Synthesis, In Vitro α-Amylase Inhibitory Activity, Molecular Docking and Structure–Activity Relationship Analysis

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5214
Author(s):  
Faisal K. Algethami ◽  
Ilyes Saidi ◽  
Hani Nasser Abdelhamid ◽  
Mohamed R. Elamin ◽  
Babiker Y. Abdulkhair ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Structure Activity Relationship ◽  
Positive Control ◽  
Activity Relationship ◽  
Major Health Problem ◽  
Relationship Analysis ◽  
Structure Activity ◽  
Hybrid Molecules ◽  
Carbohydrate Digestion

Diabetes mellitus is a major health problem globally. The management of carbohydrate digestion provides an alternative treatment. Flavonoids constitute the largest group of polyphenolic compounds, produced by plants widely consumed as food and/or used for therapeutic purposes. As such, isoxazoles have attracted the attention of medicinal chemists by dint of their considerable bioactivity. Thus, the main goal of this work was to discover new hybrid molecules with properties of both flavonoids and isoxazoles in order to control carbohydrate digestion. Moreover, the trifluoromethyl group is a key entity in drug development, due to its strong lipophilicity and metabolic stability. Therefore, the present work describes the condensation of a previously synthesized trifluoromethylated flavonol with different aryl nitrile oxides, affording 13 hybrid molecules indicated as trifluoromethylated flavonoid-based isoxazoles. The structures of the obtained compounds were deduced from by 1H NMR, 13C NMR, and HRMS analysis. The 15 newly synthesized compounds inhibited the activity of α-amylase with an efficacy ranging from 64.5 ± 0.7% to 94.7 ± 1.2% at a concentration of 50 μM, and with IC50 values of 12.6 ± 0.2 μM–27.6 ± 1.1 μM. The most effective compounds in terms of efficacy and potency were 3b, 3h, 3j, and 3m. Among the new trifluoromethylated flavonoid-based isoxazoles, the compound 3b was the most effective inhibitor of α-amylase activity (PI = 94.7 ± 1.2% at 50 μM), with a potency (IC50 = 12.6 ± 0.2 μM) similar to that of the positive control acarbose (IC50 = 12.4 ± 0.1 μM). The study of the structure–activity relationship based on the molecular docking analysis showed a low binding energy, a correct mode of interaction in the active pocket of the target enzyme, and an ability to interact with the key residues of glycosidic cleavage (GLU-230 and ASP-206), explaining the inhibitory effects of α-amylase established by several derivatives.

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