The design, synthesis, and anti-inflammatory evaluation of a drug-like library based on the natural product valerenic acid
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Author(s)
Egbewande, Folake A
Nilsson, Niclas
White, Jonathan M
Coster, Mark J
Davis, Rohan A
Year published
2017
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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 Log P, 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 ...
View more >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 Log P, 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 2.8–8.3 μM, while none of the tested compounds showed any significant effect on inhibiting TNF-α release.
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View more >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 Log P, 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 2.8–8.3 μM, while none of the tested compounds showed any significant effect on inhibiting TNF-α release.
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Journal Title
Bioorganic & Medicinal Chemistry Letters
Volume
27
Copyright Statement
© 2017 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
Subject
Medicinal and biomolecular chemistry
Organic chemistry
Organic chemistry not elsewhere classified
Pharmacology and pharmaceutical sciences