title: Efficient synthesis and biological activity of Psammaplin A and its analogues as antitumor agents.
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.
authors.affiliation: Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Suckchang
authors.initials: S
authors.lastname: Hong
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Yoonho
authors.initials: Y
authors.lastname: Shin
authors.affiliation: Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Myunggi
authors.initials: M
authors.lastname: Jung
authors.affiliation: Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Min Woo
authors.initials: MW
authors.lastname: Ha
authors.affiliation: College of Pharmacy, Inje University, 607 Obang-dong, Gimhae, Gyeongnam 621-749, South Korea.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Park
authors.affiliation: Korea Institute of Ocean Science and Technology, Global Bioresources Research Center, Ansan 426-744, South Korea.
authors.forename: Yeon-Ju
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jongheon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
authors.forename: Ki Bong
authors.initials: KB
authors.lastname: Oh
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea. Electronic address: sklee61@snu.ac.kr.
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul 151-742, South Korea. Electronic address: hgpk@snu.ac.kr.
authors.forename: Hyeung-geun
authors.initials: HG
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004220:Disulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; C098378:psammaplin A; D014443:Tyrosine
keywords: HDAC; Histone deacetylase inhibitor; Psammaplin A; Structure–activity relationship