Design and synthesis of naphthoquinone derivatives as antiproliferative agents and 20S proteasome inhibitors

  • Bioorg Med Chem Lett. 2012 Apr 15;22(8):2772-4. doi: 10.1016/j.bmcl.2012.02.086.
Kai Xu  1 ,  Zhiyan Xiao ,  Yan Bo Tang ,  Li Huang ,  Chin-Ho Chen ,  Emika Ohkoshi ,  Kuo-Hsiung Lee
Affiliations
  • 1. 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.
PMID: 22437113 DOI: 10.1016/j.bmcl.2012.02.086
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.