Niemann Britney, Puleo Amanda, Stout Conley, Markel Justin, Boone Brian A
Department of Surgery, West Virginia University, Morgantown, WV 26506, USA.
Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506, USA.
Pharmaceutics. 2022 Nov 22;14(12):2551. doi: 10.3390/pharmaceutics14122551.
Chloroquine (CQ) and Hydroxychloroquine (HCQ), initially utilized in the treatment of malaria, have now developed a long list of applications. Despite their clinical relevance, their mechanisms of action are not clearly defined. Major pathways by which these agents are proposed to function include alkalinization of lysosomes and endosomes, downregulation of C-X-C chemokine receptor type 4 (CXCR4) expression, high-mobility group box 1 protein (HMGB1) inhibition, alteration of intracellular calcium, and prevention of thrombus formation. However, there is conflicting data present in the literature. This is likely the result of the complex overlapping pathways between these mechanisms of action that have not previously been highlighted. In fact, prior research has focused on very specific portions of particular pathways without describing these in the context of the extensive CQ/HCQ literature. This review summarizes the detailed data regarding CQ/HCQ's mechanisms of action while also providing insight into the overarching themes. Furthermore, this review provides clinical context to the application of these diverse drugs including their role in malaria, autoimmune disorders, cardiovascular disease, thrombus formation, malignancies, and viral infections.
氯喹（CQ）和羟氯喹（HCQ）最初用于治疗疟疾，如今已发展出一长串应用。尽管它们具有临床相关性，但其作用机制尚未明确界定。这些药物被认为发挥作用的主要途径包括溶酶体和内体的碱化、CXC趋化因子受体4（CXCR4）表达的下调、高迁移率族蛋白B1（HMGB1）的抑制、细胞内钙的改变以及血栓形成的预防。然而，文献中存在相互矛盾的数据。这可能是由于这些作用机制之间复杂的重叠途径，而此前并未得到强调。事实上，先前的研究集中在特定途径的非常具体的部分，而没有在广泛的氯喹/羟氯喹文献背景下进行描述。本综述总结了关于氯喹/羟氯喹作用机制的详细数据，同时也深入探讨了总体主题。此外，本综述为这些不同药物的应用提供了临床背景，包括它们在疟疾、自身免疫性疾病、心血管疾病、血栓形成、恶性肿瘤和病毒感染中的作用。
