2. Academic Validation
  3. The design, synthesis, and anti-inflammatory evaluation of a drug-like library based on the natural product valerenic acid

The design, synthesis, and anti-inflammatory evaluation of a drug-like library based on the natural product valerenic acid

  • Bioorg Med Chem Lett. 2017 Jul 15;27(14):3185-3189. doi: 10.1016/j.bmcl.2017.05.021.
Folake A Egbewande 1,  Niclas Nilsson 2,  Jonathan M White 3,  Mark J Coster 1,  Rohan A Davis 4
Affiliations

Affiliations

  • 1 Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
  • 2 LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark.
  • 3 School of Chemistry and Bio21 Institute, The University of Melbourne, VIC 3010, Australia.
  • 4 Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia. Electronic address: r.davis@griffith.edu.au.
PMID: 28558967 DOI: 10.1016/j.bmcl.2017.05.021
Abstract

The plant natural product, valerenic acid (1) was chosen as a desirable scaffold for the generation of a novel screening library due to its drug-like physicochemical parameters (such as LogP, hydrogen bond donor/acceptor counts, and molecular weight). An 11-membered amide library (2-12) was subsequently generated using parallel solution-phase synthesis and Ghosez's reagent. The chemical structures of all semi-synthetic analogues (2-12) were elucidated following analysis of the NMR, MS, UV and IR data. The structures of compounds 8 and 11 were also confirmed by X-ray crystallographic analysis. All library members were evaluated for their ability to inhibit the release of IL-8 and TNF-α. Six analogues showed moderate activity in the IL-8 assay with IC50 values of 2.8-8.3μM, while none of the tested compounds showed any significant effect on inhibiting TNF-α release.

Keywords

Anti-inflammatory; Drug design; Library; Parallel synthesis; Scaffold; Valerenic acid.

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