Novel lung adenocarcinoma and nuclear factor-kappa B (NF-κB) inhibitors: synthesis and evaluation of lantadene congeners.

Abstract

The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22β-hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 μmol, respectively against TNF-α induced activation of NF-κB. The congeners 12 and 13 exhibited inhibition of IKKβ in a single-digit micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity against A549 lung cancer cells with IC50 of 0.12 and 0.08 μmol, respectively. The lead ester congeners were stable in the acidic pH, while hydrolyzed readily in the human blood plasma to release the active parent moieties.

• Authors: Sharad Kumar Suthar, Hong L Boon, Manu Sharma
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 74 Pg. 135-44 (Mar 03 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 24457265 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• NF-kappa B
• Oleanolic Acid

Topics

• Adenocarcinoma (metabolism, pathology)
• Cell Line, Tumor
• Humans
• Lung Neoplasms (metabolism, pathology)
• Magnetic Resonance Spectroscopy
• NF-kappa B (antagonists & inhibitors, metabolism)
• Oleanolic Acid (chemistry, pharmacology)
• Phosphorylation
• Spectrometry, Mass, Electrospray Ionization