Faísca Francisco, Correia Vanessa, Petrovski Željko, Branco Luís C, Rebelo-de-Andrade Helena, Santos Miguel M
LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
Antiviral Resistance Lab, Research & Development Unit, Infectious Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, IP, Av. Padre Cruz, 1649-016 Lisboa, Portugal.
Pharmaceutics. 2022 Apr 17;14(4):877. doi: 10.3390/pharmaceutics14040877.
The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2][C1SO3]2 and [HCQH2][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2][SO4]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2][GlcCOO]2. Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra- and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.
迫切需要开发针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的有效抗病毒药物，这是全球卫生的优先事项。鉴于有关重新利用羟氯喹（HCQ）来应对这种冠状病毒的初步数据，在此我们展示了七种HCQ室温离子液体（HCQ-ILs）的定量合成以及光谱和热表征，这些离子液体是通过用两当量不同极性的有机磺酸、硫酸和羧酸对碱进行直接质子化而获得的。特别是两种无毒且亲水的HCQ-ILs，即[HCQH2][C1SO3]2和[HCQH2][GlcCOO]2，与原始药物[HCQH2][SO4]相比，将病毒诱导的细胞病变效应降低了两倍。尽管这三种化合物在病毒RNA产生方面没有显著差异，但子代病毒产生受到[HCQH2][GlcCOO]2的显著影响（p < 0.05）。总体而言，数据表明HCQ-ILs的体外抗病毒活性很可能是特定分子内和分子间相互作用的结果，与其亲水或亲脂特性关系不大。这项工作为开发具有增强物理化学性质的未来新型羟氯喹离子制剂铺平了道路。
