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Cytotoxic Activity of Rearranged Drimane Meroterpenoids against Colon Cancer Cells via Down-Regulation of β‑Catenin Expression

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journal contribution
posted on 15.01.2016, 12:06 by In Hyun Hwang, Joonseok Oh, Wei Zhou, Seoyoung Park, Joo-Hyun Kim, Amar G. Chittiboyina, Daneel Ferreira, Gyu Yong Song, Sangtaek Oh, MinKyun Na, Mark T. Hamann
Colorectal cancer has emerged as a major cause of death in Western countries. Down-regulation of β-catenin expression has been considered a promising approach for cytotoxic drug formulation. Eight 4,9-friedodrimane-type sesquiterpenoids (18) were acquired using the oxidative potential of Verongula rigida on bioactive metabolites from two Smenospongia sponges. Compounds 3 and 4 contain a 2,2-dimethylbenzo­[d]­oxazol-6­(2H)-one moiety as their substituted heterocyclic residues, which is unprecedented in such types of meroterpenoids. Gauge-invariant atomic orbital NMR chemical shift calculations were employed to investigate stereochemical details with support of the application of advanced statistics such as CP3 and DP4. Compounds 2 and 8 and the mixture of 3 and 4 suppressed β-catenin response transcription (CRT) via degrading β-catenin and exhibited cytotoxic activity on colon cancer cells, implying that their anti-CRT potential is, at least in part, one of their underlying antineoplastic mechanisms.