2. Academic Validation
  3. Psammaplin A analogues with modified disulfide bond targeting histone deacetylases: Synthesis and biological evaluation

Psammaplin A analogues with modified disulfide bond targeting histone deacetylases: Synthesis and biological evaluation

  • Eur J Med Chem. 2024 May 31:275:116541. doi: 10.1016/j.ejmech.2024.116541.
Yukun Jiang 1,  Ya Tang 1,  Yuxuan Li 1,  Lu Liu 2,  Kairui Yue 1,  Xiaoyang Li 1,  Peiju Qiu 3,  Ruijuan Yin 4,  Tao Jiang 5
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
  • 2 Marine Biomedical Research Institute of Qingdao, Qingdao, 266237, China.
  • 3 Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Marine Biomedical Research Institute of Qingdao, Qingdao, 266237, China. Electronic address: peijuqiu@ouc.edu.cn.
  • 4 Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Marine Biomedical Research Institute of Qingdao, Qingdao, 266237, China. Electronic address: yinruijuan@ouc.edu.cn.
  • 5 Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.
PMID: 38851056 DOI: 10.1016/j.ejmech.2024.116541
Abstract

Psammaplin A (PsA), a symmetrical bromotyrosine-derived disulfide marine metabolite, has been reported could inhibit HDAC1/2/3 through its thiol monomer. Inspired by the disuflide bond structure of this marine natural product, we designed and synthesized a series of PsA analogues, in which the disulfide bond of PsA was replaced with diselenide bond or cyclic disulfide/diselenide/selenenylsulfide motifs. We also studied the HDAC inhibition, cell growth inhibition, and Apoptosis induction of these PsA analogues. The results showed that, all the synthetic diselenide analogues and cyclic selenenyl sulfide compounds exhibited better antiproferative activity than their counterpart of disulfide analogues. Among the prepared analogues, diselenide analogue P-503 and P-116 significantly increased the ability of inhibiting HDAC6 and induced Apoptosis and G2/M cell cycle arrest. However, cyclic selenenylsulfides analogues P-111 lost its HDAC inhibitory ability and exhibited no effect on cell cycle and Apoptosis, indicating that the anti-proliferative mechanism of cyclic selenenylsulfides analogues has changed.

Keywords

Diselenide; HDAC; Psammaplin A; Selenenylsulfide.

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