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

Abstract

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 (1–8) 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.

Naphtoquinones and Sesquiterpene Cyclopentenones from the Sponge <i>Smenospongia cerebriformis</i> with Their Cytotoxic Activity

“…The HR-ESI-MS analysis with the aid of 13 C-NMR data indicated molecular formula of 2 to be C 15 C-NMR data suggested that both compounds 2 and 1 shared the same 1,4-naphthoquinone skeleton. However, the absence of aromatic proton signals in the 1 H-NMR spectra of 2 demonstrated replacements of all proton in the 1,4-naphthoquinone skeleton.…”

“…They were illustrated formation by a five-member ring cycloaddition in the same biosynthetic pathways of sesquiterpene quinones. 13) Compounds 3-6 were reported from a Dactylospongia sponge species in early 1990s but they have not been isolated later. The relative configuration of 3 was well described by X-ray crystallographic method.…”

Anti-inflammatory Effect of Dactyloquinone B and Cyclospongiaquinone-1 Mixture in RAW264.7 Macrophage and ICR Mice

“…15 The sponge extract (3.6 kg) was subjected to silica gel vacuum liquid chromatography (VLC) eluting with a stepwise gradient of hexane/acetone/methanol/ water to provide 13 fractions (Fr. 1 to 13).…”

“…In the course of our studies aiming to identification of anti-inflammatory metabolites from marine sponges, we investigated the anti-inflammatory activity of dactyloquinone B (DQB) and cyclospongiaquinone-1 (CSQ1) mixture obtained from the previous study. 15 The inhibitory mechanism of DQB and CSQ1 mixture was investigated through the inflammatory reactions in LPSstimulated RAW264.7 macrophages and in 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema of ICR mice.…”

Epi-Leptosphaerin: A New L-Isoascorbic Acid Derivative from Marine Sponges

“…In our ongoing mission to isolate bioactive metabolites from marine sponges of the orders Verongida and Thorectidae, our earlier studies have demonstrated the antidepressant and cytotoxic activities of numerous compounds and have isolated uncommon metabolites. [8][9][10][11] A survey of the literature reveals that bromotyrosine-types of compounds are the mainstay of the Verongida chemical repertoire. One structural feature that is common to each of these is an amide bond that confers sEH inhibitory activity.…”