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Psammaplin A analogues with modified disulfide bond targeting histone deacetylases: Synthesis and biological evaluation
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2024-05-31 , 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 3 , Tao Jiang 4
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2024-05-31 , 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 3 , Tao Jiang 4
Affiliation
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Psammaplin A (), 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 analogues, in which the disulfide bond of 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 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 and significantly increased the ability of inhibiting HDAC6 and induced apoptosis and G2/M cell cycle arrest. However, cyclic selenenylsulfides analogues 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.
中文翻译：
具有修饰的二硫键靶向组蛋白脱乙酰酶的 Psammaplin A 类似物：合成和生物学评价
Psammaplin A () 是一种对称的溴酪氨酸衍生的二硫化物海洋代谢物，据报道可以通过其硫醇单体抑制 HDAC1/2/3。受这种海洋天然产物的二硫键结构的启发，我们设计并合成了一系列类似物，其中的二硫键被二硒键或环状二硫键/二硒化物/硒烯基硫基序取代。我们还研究了这些类似物的 HDAC 抑制、细胞生长抑制和细胞凋亡诱导作用。结果表明，所有合成的二硒化物类似物和环状硒基硫醚化合物均比二硫键类似物的对应物表现出更好的抗增殖活性。所制备的类似物中，二硒化物类似物显着增加了抑制HDAC6并诱导细胞凋亡和G2/M细胞周期阻滞的能力。然而，环硒基硫类似物失去了HDAC抑制能力，对细胞周期和细胞凋亡没有影响，表明环硒基硫类似物的抗增殖机制发生了变化。
更新日期：2024-05-31
中文翻译：
具有修饰的二硫键靶向组蛋白脱乙酰酶的 Psammaplin A 类似物：合成和生物学评价
Psammaplin A () 是一种对称的溴酪氨酸衍生的二硫化物海洋代谢物，据报道可以通过其硫醇单体抑制 HDAC1/2/3。受这种海洋天然产物的二硫键结构的启发，我们设计并合成了一系列类似物，其中的二硫键被二硒键或环状二硫键/二硒化物/硒烯基硫基序取代。我们还研究了这些类似物的 HDAC 抑制、细胞生长抑制和细胞凋亡诱导作用。结果表明，所有合成的二硒化物类似物和环状硒基硫醚化合物均比二硫键类似物的对应物表现出更好的抗增殖活性。所制备的类似物中，二硒化物类似物显着增加了抑制HDAC6并诱导细胞凋亡和G2/M细胞周期阻滞的能力。然而，环硒基硫类似物失去了HDAC抑制能力，对细胞周期和细胞凋亡没有影响，表明环硒基硫类似物的抗增殖机制发生了变化。
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