Synthesis and biological evaluation of curcumin derivatives modified with α-amino boronic acid as proteasome inhibitors. Issue 14 (1st August 2018)

• Record Type: Journal Article
• Authors: Zhang, Wenjie; Bai, Heyuan; Han, Liqiang; Zhang, Han; Xu, Bo; Cui, Jingrong; Wang, Xin; Ge, Zemei; Li, Runtao
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 14(2018)
• Page Start: 2459
• Page End: 2464
• Publication Date: 2018-08-01
• Subjects: Curcumin derivatives -- Proteasome inhibitors -- α-Amino boronic acid -- Antitumor activity -- Subunit selectivity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.06.004
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Synthesized two series of curcumin derivatives with α-amino boronic acids warhead. Most compounds exhibited excellent activity over HCT116 comparing to curcumin. CompoundII-2F has a more outstanding activity against ChT-L. CompoundII-2F is a proteasome inhibitor with high subunit selectivity. Abstract: Curcumin is a well-known pharmacophore and some of its derivatives are shown to target 20S proteasome recently. In this report, we designed and synthesized two series of curcumin derivatives modified with different α-amino boronic acids as potent proteasome inhibitors. The synthesized compounds were evaluated for their cytotoxic activities against HCT116 cells, and the results showed that all of them exhibited excellent cell growth inhibitory activity comparing with curcumin, with the IC50 values varying from 0.17 μM to 1.63 μM. CompoundII-2F with free boronic acid was assayed for its proteasome inhibitory activity and the results indicated thatII-2F exhibited more potent inhibitory activity against ChT-L with high subunit selectivity than any other reported curcumin derivatives.