title: Design and synthesis of naphthoquinone derivatives as antiproliferative agents and 20S proteasome inhibitors.
abstract: Fourteen naphthoquinone derivatives (1-14) were designed based on a putative proteasome inhibitor PI-083. These compounds were synthesized and evaluated against A549, DU145, KB, and KBvin tumor cell lines. Six compounds (2, 4, 8, 9, 10, and 13) showed antiproliferative activities comparable to that of PI-083. Among them, compound 8 was confirmed as a 20S proteasome inhibitor in both in vitro and cell-based assays. These findings endorse further optimization efforts based on this structural phenotype to develop potential anticancer drug candidates.
authors.affiliation: Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Xiao
authors.forename: Yan Bo
authors.initials: YB
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Chin-Ho
authors.initials: CH
authors.lastname: Chen
authors.forename: Emika
authors.initials: E
authors.lastname: Ohkoshi
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D018943:Anthracyclines / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D061988:Proteasome Inhibitors
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D009285:Naphthoquinones; D061988:Proteasome Inhibitors; C058288:PI 083