Studying Histone Deacetylase Inhibition and Apoptosis Induction of Psammaplin A Monomers with Modified Thiol Group

Yu Bao; Qihao Xu; Lin Wang; Yunfei Wei; Baichun Hu; Jian Wang; Dan Liu; Linxiang Zhao; Yongkui Jing

doi:10.1021/acsmedchemlett.0c00369

Studying Histone Deacetylase Inhibition and Apoptosis Induction of Psammaplin A Monomers with Modified Thiol Group

ACS Med Chem Lett. 2021 Jan 5;12(1):39-47. doi: 10.1021/acsmedchemlett.0c00369. eCollection 2021 Jan 14.

Authors

Yu Bao¹, Qihao Xu², Lin Wang¹, Yunfei Wei², Baichun Hu², Jian Wang², Dan Liu², Linxiang Zhao², Yongkui Jing¹

Affiliations

¹ Department of Pharmacology, Liaoning Key Lab of Targeting Drugs for Hematological Malignancies, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, R. P. China.
² Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, China.

Abstract

Psammaplin A (PsA) is a bromotyrosine disulfide dimer with histone deacetylase (HDAC) inhibition and acts through reduced monomer PsA-SH. We studied the connection of HDAC inhibition, cell growth inhibition, and apoptosis induction of PsA-SH by modifying the -SH group with deletion (6a) or replacement with hydroxamic acid (10b) or benzamide (12g). PsA-SH inhibits HDAC1/2/3 and 6a loses the HDAC inhibition ability. 10b inhibits HDAC1/2/3/6 while 12g shows selective inhibition of HDAC3. PsA-SH and 10b, but neither 6a nor 12g, induce apoptosis in human leukemia HL-60 cells associated with increased acetylation of Histone H3. PsA-SH and 10b inhibit growth of several solid tumor cell lines in vitro and Lewis lung cancer cell growth in vivo. PsA-SH is a simple scaffold for developing selective HDAC inhibitors and induces apoptosis through inhibiting HDAC1/2.