Hydroxychloroquine Sulfate is a synthetic 4-aminoquinoline derivative that serves as an antimalarial drug. Hydroxychloroquine Sulfate exerts its antimalarial effect by targeting the heme metabolism pathway in Plasmodium, disrupting the polymerization of toxic heme and ultimately causing parasite death[1]. Beyond antimalarial activity, Hydroxychloroquine Sulfate is widely in the research of autoimmune diseases (e.g., rheumatoid arthritis[2], systemic lupus erythematosus[3]), as well as cancer and COVID-19[4][5].
In vitro, treatment of SARS-CoV-2-infected Vero cells with chloroquine or Hydroxychloroquine Sulfate (0.032–100μM) for 24–48 hours decreased the viral replication in a concentration-dependent manner, and Hydroxychloroquine Sulfate(EC50=0.72μM) was found to be more potent than chloroquine (EC50=5.47μM)[6]. Pretreatment of RAW 264.7 cells with 5μM Hydroxychloroquine Sulfate for 2h potently inhibited CpG2006 DNA-induced NF-κB activation (IC50=1.2μM, >95% suppression) and showed superior selectivity for nucleic acid ligands (EC50=1.4μM for RNA40) over small-molecule agonist R-848 (EC50 >10μM)[7].
In vivo, Hydroxychloroquine Sulfate (60mg/kg; oral; 5 times/week for 7 weeks) significantly reduced serum anti-dsDNA antibody titers by 40% (p<0.05 vs. control) in MRL/lpr mice, but had no significant effect on proteinuria or survival.Pretreatment with Hydroxychloroquine Sulfate (20mg/kg; oral; 18 h) reversed CpG1668-induced serum IL-6 elevation by >60%[7].
References:
[1] Caminal-Montero, L., & Suárez-Díaz, S. (2019). Hydroxychloroquine and Antimalarials. The Journal of rheumatology, 46(11), 1547.
[2] Schrezenmeier, E., & Dörner, T. (2020). Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nature reviews. Rheumatology, 16(3), 155–166.
[3] Ponticelli, C., & Moroni, G. (2017). Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert opinion on drug safety, 16(3), 411–419.
[4] Ferreira, P. M. P., Sousa, R. W. R., Ferreira, J. R. O., Militão, G. C. G., & Bezerra, D. P. (2021). Chloroquine and hydroxychloroquine in antitumor therapies based on autophagy-related mechanisms. Pharmacological research, 168, 105582.
[5] Sinha, N., & Balayla, G. (2020). Hydroxychloroquine and COVID-19. Postgraduate medical journal, 96(1139), 550–555.
[6] Yao, X., Ye, F., Zhang, M., Cui, C., Huang, B., Niu, P., Liu, X., Zhao, L., Dong, E., Song, C., Zhan, S., Lu, R., Li, H., Tan, W., & Liu, D. (2020). In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 71(15), 732–739.
[7] Lamphier, M., Zheng, W., Latz, E., Spyvee, M., Hansen, H., Rose, J., Genest, M., Yang, H., Shaffer, C., Zhao, Y., Shen, Y., Liu, C., Liu, D., Mempel, T. R., Rowbottom, C., Chow, J., Twine, N. C., Yu, M., Gusovsky, F., & Ishizaka, S. T. (2014). Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo.
Hydroxychloroquine Sulfate是一种合成的4-氨基喹啉衍生物类抗疟药。Hydroxychloroquine Sulfate通过靶向疟原虫的血红素代谢通路，干扰毒性血红素的聚合过程，导致寄生虫死亡[1]。除抗疟作用外，Hydroxychloroquine Sulfate还被广泛应用于自身免疫性疾病（如类风湿关节炎[2]、系统性红斑狼疮[3]）、癌症和COVID-19的研究[4][5]。
体外实验中，用chloroquine或Hydroxychloroquine Sulfate（0.032–100μM）处理SARS-CoV-2感染的Vero细胞24–48小时，可浓度依赖性地抑制病毒复制，且Hydroxychloroquine Sulfate（EC50 = 0.72μM）的抗病毒活性显著强于chloroquine（EC50 = 5.47μM）[6]。此外，在RAW 264.7细胞中，5μM Hydroxychloroquine Sulfate预处理2小时能强效抑制CpG2006 DNA诱导的NF-κB激活（IC50 = 1.2μM，抑制率>95%），并对核酸配体（RNA40的EC50 = 1.4μM）表现出比小分子激动剂R-848（EC50 >10μM）更高的选择性拮抗作用[7]。
体内实验中，Hydroxychloroquine Sulfate（60 mg/kg；口服；每周5次；连续7周）可使MRL/lpr自发性狼疮小鼠血清抗双链DNA抗体滴度显著降低40%（p < 0.05 vs. 对照组），但对蛋白尿或生存率无显著影响；而以20mg/kg Hydroxychloroquine Sulfate口服预处理18小时则可逆转CpG1668诱导的小鼠血清IL-6升高（抑制率>60%）[7]。