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2000
Volume 21, Issue 5
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Background

Hyperlipidemia is characterized by an abnormally elevated serum cholesterol, triglycerides, or both. The relationship between an elevated level of LDL and cardiovascular diseases is well-established. Cholesteryl ester transfer protein (CETP) is an enzyme that moves cholesterol esters and triglycerides between LDL, VLDL, and HDL. CETP inhibition leads to a reduction in cardiovascular disease by raising HDL and minimizing LDL.

Objective

This study synthesized ten -chlorinated benzene sulfonamides 6a-6j and explored their structure-activity relationship.

Methods

The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR, and HR-MS. Moreover, cheminformatics analyses included pharmacophore mapping, LibDock studies, and cheminformatics characterization using 2-dimensional (2D) molecular descriptors and principal component analysis.

Results

Based on functional CETP assays, compounds , , and demonstrated the strongest inhibitory activities against CETP, reaching 100% inhibition. The inhibitory activity of compounds - and - ranged from 47.5% to 96.5% at 10 µM concentration. Pharmacophore mapping results suggested CETP inhibitory action, while the docking scores and calculated binding energies predicted favoring binding at the CETP active site. Best-scoring docking poses predicted critical hydrophobic features corresponding to key interactions with His232 and Cys13. Cheminformatics analysis using 2D molecular descriptors indicated that the synthesized compounds span various physicochemical properties and drug-likeness.

Conclusion

It was found that a chloro moiety at the -position, or a nitro group at the and -positions, improves the CETP inhibitory activity of synthesized analogs. Computational studies suggest the formation of stable ligand-protein complexes between compounds - and CETP.

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Chemical Synthesis, Biological Evaluation, and Cheminformatics Analysis of a Group of Chlorinated Diaryl Sulfonamides: Promising Inhibitors of Cholesteryl Ester Transfer Protein
Curr. Computeraided Drug Des. 21, 694 (2025); https://doi.org/10.2174/0115734099292078240218095540
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  • Article Type:     Research Article
Keyword(s): Cardiovascular diseases; cheminformatics; chlorinated sulfonamides; cholesteryl ester transfer protein (CETP); docking; pharmacophore mapping

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