Laboratoire de Parasitologie-Mycologie, Centre de Biologie Humaine, CHU Amiens Picardie - site Sud, Amiens, France.
Agents Infectieux, Résistance et Chimiothérapie (AGIR), UR 4294, Université de Picardie Jules Verne, UFR de Pharmacie, Amiens, France.
ChemMedChem. 2021 Jul 20;16(14):2192-2194. doi: 10.1002/cmdc.202100176. Epub 2021 May 1.
Despite considerable efforts, malaria remains one of the most devastating infectious disease worldwide. In the absence of an effective vaccine, the prophylaxis and management of Plasmodium infections still rely on the therapeutic use of antimalarial agents. However, the emergence of resistant parasites has jeopardized the efficiency of virtually all antimalarial drugs, including artemisinin combination therapies (ACTs). Thus, there is an urgent need for innovative treatments with novel targets to avoid or overcome drug resistance. In this context, Huang & colleagues prioritized compounds that can block the activity of epigenetic enzymes, and described the discovery of a selective P. falciparum histone deacetylase (HDAC) inhibitor with high activity against various stages of the parasite. These findings may pave the way toward developing new lead compounds with broad-spectrum activity, thus facilitating malaria treatment and elimination.
尽管付出了巨大努力,疟疾仍然是全球最具破坏性的传染病之一。在缺乏有效疫苗的情况下,预防和管理疟原虫感染仍然依赖于抗疟药物的治疗用途。然而,耐药寄生虫的出现危及到几乎所有抗疟药物的疗效,包括青蒿素联合疗法(ACT)。因此,迫切需要具有新靶标的创新疗法来避免或克服耐药性。在这种情况下,Huang 及其同事优先考虑能够阻断表观遗传酶活性的化合物,并描述了一种选择性的疟原虫组蛋白去乙酰化酶(HDAC)抑制剂的发现,该抑制剂对寄生虫的各个阶段均具有高活性。这些发现可能为开发具有广谱活性的新先导化合物铺平道路,从而促进疟疾的治疗和消除。