title: Synthesis of chiral hydroxylated enones as potential anti-tumor agents.
abstract: A series of chiral hydroxylated enones were synthesized as COTC ether analogues to investigate the structural features required for optimal and selective anti-tumor activity. The cytotoxicity of the seven COTC ether analogues against WRL-68 normal and HepG2, HL-60 cancer cell lines were measured. C-4 ether analogues with an aliphatic chain substituent were found to be more favorable than their aromatic counterparts. Inversion of the configuration at C-4 in 5e to give 5f only resulted in reduced selectivity towards cancer cells. These results show that 4-O-pentyl-gabosine D (5e) has optimum selectivity and cytotoxicity towards two cancer cell lines.
authors.affiliation: Department of Chemistry and Center of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, Hong Kong, China. tonyshing@cuhk.edu.hk
authors.forename: Tony K M
authors.initials: TK
authors.lastname: Shing
authors.forename: Ho T
authors.initials: HT
authors.lastname: Wu
authors.forename: H F
authors.initials: HF
authors.lastname: Kwok
authors.forename: Clara B S
authors.initials: CB
authors.lastname: Lau
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D006900:Hydroxylation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003512:Cyclohexanones; C011202:2-crotonyloxymethyl-(4R,5R,6R)-4,5,6-trihydroxycyclohex- 2-enone