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

作者：Suthar Sharad Kumar; Boon Hong L; Sharma Manu^*

来源：European Journal of Medicinal Chemistry, 2014, 74: 135-144.

DOI：10.1016/j.ejmech.2013.12.052

• Tumor necrosis factor-alpha
• Nuclear factor-kappa B
• Inhibitor of nuclear factor-kappa B kinase beta
• A549 lung cancer cells
• Lantadene congeners

The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22 beta hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-kappa B and IKK beta inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 mu mol, respectively against TNF-alpha. induced activation of NF-kappa B. The congeners 12 and 13 exhibited inhibition of IKK beta 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 mu mol, 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.

• 出版日期2014-3-3