title: Synthesis and cytotoxicity of some rigid derivatives of methyl 2,5-dihydroxycinnamate.
abstract: Eight rigid compounds designed as esterase-stable analogues of methyl 2,5-dihydroxycinnamate (1) were synthesized. These derivatives include 2-(2',5'-dihydroxybenzylidene)cyclopentenone (3a), 2-(2',5'-dihydroxybenzylidene)cyclohexanone (3b), 2,6-bis(2',5'-dihydroxybenzylidene)cyclohexanone (4b), 2,6-bis(2',5'-dihydroxybenzylidene)cyclopentenone (4a), (E)-3-(2',5'-dihydroxybenzylidene)pyrrolidin-2-one (5), (E)-5-(2',5'-dihydroxybenzylidene)-1,2-isothiazolidine-1,1-dioxide (6), 4-(2',5'-dihydroxyphenyl)-5H-furan-2-one (7), and 3-(2',5'-dihydroxyphenyl)cyclopent-2-ene-1-one (8). Among the eight compounds, the furanone 7 and cyclopentenone 8 showed the most potent cytotoxicity with IC50 values of 0.39-0.98 microg/mL. Compound 8 was further brominated, phenylated and methylated at the alpha position to give three corresponding analogues, including 2-bromo-3-(2',5'-dihydroxyphenyl)cyclopent-2-ene-1-one (24), 3-(2',5'-dihydroxyphenyl)-2-phenylcyclopent-2-ene-1-one (27), and 3-(2',5'-dihydroxyphenyl)-2-methylcyclopent-2-ene-1-one (28). Among the three, the most enhanced activity was observed with the phenylated compound 27.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: Nguyen-Hai
authors.initials: NH
authors.lastname: Nam
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: You
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Hong
authors.forename: Hwan-Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Byung-Zun
authors.initials: BZ
authors.lastname: Ahn
mesh_terms: D000818:Animals; D002934:Cinnamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D051379:Mice
chemical_list: D002934:Cinnamates; C067472:methyl 2,5-dihydroxycinnamate