Discovery of 1,3-Disubstituted 2,5-Diketopiperazine Derivatives as Potent Class I HDACs Inhibitors.

Discovery of 1,3-Disubstituted 2,5-Diketopiperazine Derivatives as Potent Class I HDACs Inhibitors. Chem Pharm Bull (Tokyo). 2020;68(5):466-472 Authors: Gong G, Qi J, Lv Y, Dong S, Cao C, Li D, Zhao R, Li Z, Chen X Abstract Histone deacetylases (HDACs) as attractive targets in many diseases therapies has been studied extensively, and its application in cancer research is the most important. Here, we developed a series of derivatives containing natural 2,5-diketopiperazine (DKP) skeleton. Several compounds exhibited distinct HDAC1 inhibitory activities, in particular 2a (IC50 = 405 nM). The selectivity profile for representative 2a indicated that this series of compounds had a preference for HDAC1-3. Additionally, 2a showed the best growth inhibitory activities against K562 and HL-60 tumor cell line with IC50 values of 4.23 and 4.16 µM, respectively. This work may lay the foundation for developing DKP-based HDAC inhibitors as a potential anticancer agent. PMID: 32378544 [PubMed - in process]
Source: Chemical and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Chem Pharm Bull (Tokyo) Source Type: research