title: Structure-activity relationship of C5-curcuminoids and synthesis of their molecular probes thereof.
abstract: A series of novel analogues of 1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-(1E,4E)-1,4-dien-3-one (C(5)-curcumin), which is a natural analogue of curcumin isolated from the rhizomes of Curcuma domestica Val. (Zingiberacea), were synthesized and evaluated for their cytotoxicities against human colon cancer cell line HCT-116 to conclude the SAR of C(5)-curcuminoids for further development of their use in cancer chemotherapy: (1) Bis(arylmethylidene)acetone serves as a promising skeleton for eliciting cytotoxicity. (2) The 3-oxo-1,4-pentadiene structure is essential for eliciting cytotoxicity. (3) As for the extent of the aromatic substituents, hexasubstituted compounds exhibit strong activities, in which 3,4,5-hexasubstitution results in the highest potency. (5) The symmetry between two aryl rings is not an essential requirement for bis(arylmethylidene)acetones to elicit cytotoxicity. (6) para-Positions allows the installation of additional functional groups for use as molecular probes. By taking advantage of the SAR diagram, we have elaborated several advanced derivatives having GI(50) of single-digit micromolar potencies that will function as molecular probes to target and/or report key biomolecules interacting with curcumin and C(5)-curcumin.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aobayama, Sendai, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamakoshi
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Ohori
authors.forename: Chieko
authors.initials: C
authors.lastname: Kudo
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sato
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanoh
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shibata
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Iwabuchi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin