Flavonoid analogues as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation

Honghui Liu; Yan Wang; Mingxia Lv; Yi Luo; Bu-Ming Liu; Yan Huang; Mian Wang; Jianyi Wang

doi:10.1016/j.bioorg.2020.104370

Flavonoid analogues as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation

Bioorg Chem. 2020 Dec:105:104370. doi: 10.1016/j.bioorg.2020.104370. Epub 2020 Oct 12.

Authors

Honghui Liu¹, Yan Wang², Mingxia Lv³, Yi Luo⁴, Bu-Ming Liu⁵, Yan Huang⁵, Mian Wang⁶, Jianyi Wang⁷

Affiliations

¹ Medical College, Guangxi University, Nanning 530004, China; School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.
² College of Life Science and Technology, Guangxi University, Nanning 530004, China.
³ Medical College, Guangxi University, Nanning 530004, China.
⁴ Guangxi Institute for Food and Drug Control, Nanning 530021, China.
⁵ Guangxi Key Laboratory of Traditional Chinese Medicine, Quality Standards, Nanning 530022, China.
⁶ College of Life Science and Technology, Guangxi University, Nanning 530004, China. Electronic address: mianwang@gxu.edu.cn.
⁷ Medical College, Guangxi University, Nanning 530004, China; School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China. Electronic address: jianyiwang@gxu.edu.cn.

PMID: 33096309
DOI: 10.1016/j.bioorg.2020.104370

Abstract

A series of novel flavonoid analogues were designed and synthesized. The aimed compounds for urease inhibitory activities were clearly superior to the control drug thiourea (more than 10 times). Among these compounds, L2 (IC₅₀ = 1.343 µM) and L12 (IC₅₀ = 1.207 µM) exhibited the most excellent urease inhibitory activity in vitro. The molecular dockings of L2, L12 and L22 into urease were performed to explore the binding modes and their structure-activity relationship. Furthermore, these aimed compounds showed good druggable properties.

Keywords: Docking; Druggability; Flavonoid analogues; Synthesis; Urease inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Canavalia / enzymology
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Flavonoids / chemical synthesis
Flavonoids / chemistry
Flavonoids / pharmacology*
Molecular Docking Simulation*
Molecular Structure
Structure-Activity Relationship
Urease / antagonists & inhibitors*
Urease / metabolism

Substances

Enzyme Inhibitors
Flavonoids
Urease