2. Academic Validation
  3. Identification and synthesis of selective cholesterol esterase inhibitor using dynamic combinatorial chemistry

Identification and synthesis of selective cholesterol esterase inhibitor using dynamic combinatorial chemistry

  • Bioorg Chem. 2022 Feb;119:105520. doi: 10.1016/j.bioorg.2021.105520.
Shuang Zhao 1,  Yao Wu 1,  Lei Hu 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Jiangsu University, Zhenjiang, 301 Xuefu Rd., Zhenjiang, China.
  • 2 School of Pharmacy, Jiangsu University, Zhenjiang, 301 Xuefu Rd., Zhenjiang, China. Electronic address: [email protected].
PMID: 34864280 DOI: 10.1016/j.bioorg.2021.105520
Abstract

In this study, the concept of dynamic combinatorial chemistry (DCC) was applied to explore novel Cholesterol esterase (CEase) inhibitors. In the presence of Enzyme, two substrates (A1H3 and A2H3) were amplified from the dynamic combinatorial library (DCL), which was generated through reversible acylhydrazone formation reaction. In the in vitro biological evaluation, compound A1H3 exhibited not only potent (IC50 in nanomolar range) but also selective inhibition (>120 folds of selectivity for CEase over AChE). Furthermore, the binding pattern and possible binding mechanism were investigated in the kinetic experiment and molecular docking study, respectively.

Keywords

Cholesterol esterase; Dynamic combinatorial chemistry; Enzyme inhibition; Kinetic study; Molecular docking.

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