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Synthesis and Identification of Novel Berberine Derivatives as Potent Inhibitors against TNF-α-Induced NF-κB Activation

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
Authors to whom correspondence should be addressed.
These authors made equal contribution to this work.
Molecules 2017, 22(8), 1257;
Received: 27 June 2017 / Revised: 24 July 2017 / Accepted: 25 July 2017 / Published: 27 July 2017
(This article belongs to the Special Issue Anti-inflammatory Agents)
PDF [5407 KB, uploaded 27 July 2017]


Twenty-three new berberine (BBR) analogues defined on substituents of ring D were synthesized and evaluated for their activity for suppression of tumor necrosis factor (TNF)-α-induced nuclear factor (NF)-κB activation. Structure–activity relationship (SAR) analysis indicated that suitable tertiary/quaternary carbon substitutions at the 9-position or rigid fragment at position 10 might be beneficial for enhancing their anti-inflammatory potency. Among them, compounds 2d, 2e, 2i and 2j exhibited satisfactory inhibitory potency against NF-κB activation, with an inhibitory rate of around 90% (5 μM), much better than BBR. A preliminary mechanism study revealed that all of them could inhibit TNF-α-induced NF-κB activation via impairing IκB kinase (IKK) phosphorylation as well as cytokines interleukin (IL)-6 and IL-8 induced by TNF-α. Therefore, the results provided powerful information on further structural modifications and development of BBR derivatives into a new class of anti-inflammatory candidates for the treatment of inflammatory diseases. View Full-Text
Keywords: berberine; anti-inflammatory; NF-κB; IκB kinase; structure-activity relationship berberine; anti-inflammatory; NF-κB; IκB kinase; structure-activity relationship

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Wang, Y.-X.; Liu, L.; Zeng, Q.-X.; Fan, T.-Y.; Jiang, J.-D.; Deng, H.-B.; Song, D.-Q. Synthesis and Identification of Novel Berberine Derivatives as Potent Inhibitors against TNF-α-Induced NF-κB Activation. Molecules 2017, 22, 1257.

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