2. Academic Validation
  3. Efficient synthesis and biological activity of Psammaplin A and its analogues as antitumor agents

Efficient synthesis and biological activity of Psammaplin A and its analogues as antitumor agents

  • Eur J Med Chem. 2015:96:218-30. doi: 10.1016/j.ejmech.2015.04.001.
Suckchang Hong 1,  Yoonho Shin 2,  Myunggi Jung 1,  Min Woo Ha 1,  Yohan Park 3,  Yeon-Ju Lee 4,  Jongheon Shin 2,  Ki Bong Oh 5,  Sang Kook Lee 6,  Hyeung-geun Park 7
Affiliations

Affiliations

  • 1 Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
  • 2 Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
  • 3 College of Pharmacy, Inje University, 607 Obang-dong, Gimhae, Gyeongnam 621-749, South Korea.
  • 4 Korea Institute of Ocean Science and Technology, Global Bioresources Research Center, Ansan 426-744, South Korea.
  • 5 Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
  • 6 Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea. Electronic address: sklee61@snu.ac.kr.
  • 7 Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul 151-742, South Korea. Electronic address: hgpk@snu.ac.kr.
PMID: 25884112 DOI: 10.1016/j.ejmech.2015.04.001
Abstract

We describe a new concise method for the synthesis of psammaplin A and its analogues, and antitumor activity of psammaplin A analogues. Psammaplin A was obtained with 41% yield in 5 steps from 3-bromo-4-hydroxybenzaldahyde and ethyl acetoacetate via Knoevenagel condensation and α-nitrosation as key steps. Twenty eight analogues of psammaplin A were prepared employing the new synthetic approach. Structure-activity relationship study against cytotoxicity reveal that the free oxime group and disulfide functional group were responsible for high cytotoxicity. Also the bromotyrosine component was relatively tolerable and hydrophobic aromatic groups preserved the cytotoxicity. The cytotoxicity of aromatic group is dependent on the size and spatial geometry. Among them, five compounds showed comparable cytotoxicity to psammaplin A. Compound 30 exhibited potential HDAC inhibitory activity and in vivo antitumor activity.

Keywords

HDAC; Histone deacetylase inhibitor; Psammaplin A; Structure–activity relationship.

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