Department of Chemistry and Technologies of Drugs, Sapienza University of Rome, P. le A. Moro 5, 00185, Rome, Italy.
Department of Chemistry and Technologies of Drugs, Sapienza University of Rome, P. le A. Moro 5, 00185, Rome, Italy.
Curr Opin Chem Biol. 2020 Aug;57:65-74. doi: 10.1016/j.cbpa.2020.05.008. Epub 2020 Jun 29.
Histone modifying enzymes have vital roles in the growth and survival of both parasites and humans. Targeting the epigenome can be a new strategy for the treatment of parasitic diseases. Compounds modulating histone acetylation/deacetylation have recently been reported hampering Plasmodium, Schistosoma, Leishmania, and Trypanosoma infections. Beside new histone deacetylase inhibitors, PfGCN5 and bromodomain inhibitors have been recently described to inhibit Plasmodium proliferation. Sm histone deacetylase 8 and SmSIRT2, as well as Leishmania and Trypanosoma sirtuins (SIR2rps), seem to be the most reliable targets to effectively fight the related protozoan infections. The selectivity toward parasite over mammalian cells is still an open question, and significant optimization efforts of epidrugs are still required to improve potency/selectivity and decrease toxicity. Recent reports on the alteration of cellular signaling pathways provoked by parasite infection through changes in the host acetylation/deacetylation status at gene promoters may suggest novel therapeutic strategies to treat these diseases.
组蛋白修饰酶在寄生虫和人类的生长和存活中起着至关重要的作用。针对表观基因组可能是治疗寄生虫病的新策略。最近有报道称，调节组蛋白乙酰化/去乙酰化的化合物可干扰疟原虫、血吸虫、利什曼原虫和锥虫感染。除了新的组蛋白去乙酰化酶抑制剂外，PfGCN5 和溴结构域抑制剂最近也被描述为可抑制疟原虫增殖。Sm 组蛋白去乙酰化酶 8 和 SmSIRT2 以及利什曼原虫和锥虫 SIR2rps（SIR2rps）似乎是有效对抗相关原生动物感染的最可靠靶点。对寄生虫相对于哺乳动物细胞的选择性仍然是一个悬而未决的问题，仍然需要对表皮药物进行大量的优化工作，以提高效力/选择性并降低毒性。最近有报道称，寄生虫感染通过改变宿主基因启动子处的乙酰化/去乙酰化状态改变细胞信号通路，这可能提示治疗这些疾病的新的治疗策略。
