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

Kai Xu; Zhiyan Xiao; Yan Bo Tang; Li Huang; Chin-Ho Chen; Emika Ohkoshi; Kuo-Hsiung Lee

doi:10.1016/j.bmcl.2012.02.086

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. Epub 2012 Mar 2.

Authors

Kai Xu¹, Zhiyan Xiao, Yan Bo Tang, Li Huang, Chin-Ho Chen, Emika Ohkoshi, Kuo-Hsiung Lee

Affiliation

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anthracyclines / chemistry
Anthracyclines / pharmacology
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Design*
Drug Screening Assays, Antitumor
Humans
Inhibitory Concentration 50
Models, Molecular
Molecular Structure
Naphthoquinones / chemical synthesis*
Naphthoquinones / chemistry
Naphthoquinones / pharmacology
Proteasome Inhibitors*

Substances

Anthracyclines
Antineoplastic Agents
Naphthoquinones
Proteasome Inhibitors
PI 083