Synthesis and cytotoxicity of some rigid derivatives of methyl 2,5-dihydroxycinnamate.
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.
Nam
Nguyen-Hai
NH
College of Pharmacy, Chungnam National University, Daejeon, Korea.
Kim
Yong
Y
You
Young-Jae
YJ
Hong
Dong-Ho
DH
Kim
Hwan-Mook
HM
Ahn
Byung-Zun
BZ
D000818:Animals; D002934:Cinnamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D051379:Mice
D002934:Cinnamates; C067472:methyl 2,5-dihydroxycinnamate