Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Synthesis and Cytotoxicity of Some Rigid Derivatives of Methyl 2,5-Dihydroxycinnamate

  • Nam, Nguyen-Hai (College of Pharmacy, Chungnam National University) ;
  • Kim, Yong (College of Pharmacy, Chungnam National University) ;
  • You, Young-Jae (College of Pharmacy, Chungnam National University) ;
  • Hong, Dong-Ho (College of Pharmacy, Chungnam National University, Research Institute of Biosciences and Biotechnology) ;
  • Kim, Hwan-Mook (Research Institute of Biosciences and Biotechnology) ;
  • Ahn, Byung-Zun (College of Pharmacy, Chungnam National University)
  • Published : 2002.10.01
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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'-dihydroxybenzy-lidene)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 $IC_{50}$ values of 0.39-0.98 $\mu\textrm{g}$/mL. Compound 8 was further brominated, phenylated and methylated at the a 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.

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References

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