title: 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.
authors.affiliation: †Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United States.
authors.forename: In Hyun
authors.initials: IH
authors.lastname: Hwang
authors.forename: Joonseok
authors.initials: J
authors.lastname: Oh
authors.affiliation: §College of Pharmacy, Chungnam National University, Yuseong-gu, Daejeon 305-764, Republic of Korea.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: ⊥Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Seoyoung
authors.initials: S
authors.lastname: Park
authors.affiliation: ⊥Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Amar G
authors.initials: AG
authors.lastname: Chittiboyina
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: §College of Pharmacy, Chungnam National University, Yuseong-gu, Daejeon 305-764, Republic of Korea.
authors.forename: Gyu Yong
authors.initials: GY
authors.lastname: Song
authors.affiliation: ⊥Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Sangtaek
authors.initials: S
authors.lastname: Oh
authors.affiliation: §College of Pharmacy, Chungnam National University, Yuseong-gu, Daejeon 305-764, Republic of Korea.
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
authors.forename: Mark T
authors.initials: MT
authors.lastname: Hamann
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051176:beta Catenin / Q000187:drug effects / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; D013729:Terpenes; D051176:beta Catenin; C437376:drimane