Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2
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 cha...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/4/877 |
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| author | Francisco Faísca Vanessa Correia Željko Petrovski Luís C. Branco Helena Rebelo-de-Andrade Miguel M. Santos |
| author_facet | Francisco Faísca Vanessa Correia Željko Petrovski Luís C. Branco Helena Rebelo-de-Andrade Miguel M. Santos |
| author_sort | Francisco Faísca |
| collection | DOAJ |
| description | 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, [HCQH<sub>2</sub>][C<sub>1</sub>SO<sub>3</sub>]<sub>2</sub> and [HCQH<sub>2</sub>][GlcCOO]<sub>2</sub>, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH<sub>2</sub>][SO<sub>4</sub>]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (<i>p</i> < 0.05) by [HCQH<sub>2</sub>][GlcCOO]<sub>2</sub>. 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. |
| first_indexed | 2024-03-09T10:30:24Z |
| format | Article |
| id | doaj.art-b8e4f34bf4c34fe6abb3fa56e62e4237 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T10:30:24Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b8e4f34bf4c34fe6abb3fa56e62e42372023-12-01T21:19:08ZengMDPI AGPharmaceutics1999-49232022-04-0114487710.3390/pharmaceutics14040877Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2Francisco Faísca0Vanessa Correia1Željko Petrovski2Luís C. Branco3Helena Rebelo-de-Andrade4Miguel M. Santos5LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, PortugalAntiviral Resistance Lab, Research & Development Unit, Infectious Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, IP, Av. Padre Cruz, 1649-016 Lisboa, PortugalLAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, PortugalLAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, PortugalAntiviral Resistance Lab, Research & Development Unit, Infectious Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, IP, Av. Padre Cruz, 1649-016 Lisboa, PortugalLAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, PortugalThe 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, [HCQH<sub>2</sub>][C<sub>1</sub>SO<sub>3</sub>]<sub>2</sub> and [HCQH<sub>2</sub>][GlcCOO]<sub>2</sub>, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH<sub>2</sub>][SO<sub>4</sub>]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (<i>p</i> < 0.05) by [HCQH<sub>2</sub>][GlcCOO]<sub>2</sub>. 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.https://www.mdpi.com/1999-4923/14/4/877API-ILsCOVID-19hydroxychloroquinepharmaceutical ionic liquidsSARS-CoV-2 |
| spellingShingle | Francisco Faísca Vanessa Correia Željko Petrovski Luís C. Branco Helena Rebelo-de-Andrade Miguel M. Santos Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2 Pharmaceutics API-ILs COVID-19 hydroxychloroquine pharmaceutical ionic liquids SARS-CoV-2 |
| title | Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2 |
| title_full | Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2 |
| title_fullStr | Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2 |
| title_full_unstemmed | Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2 |
| title_short | Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2 |
| title_sort | enhanced in vitro antiviral activity of hydroxychloroquine ionic liquids against sars cov 2 |
| topic | API-ILs COVID-19 hydroxychloroquine pharmaceutical ionic liquids SARS-CoV-2 |
| url | https://www.mdpi.com/1999-4923/14/4/877 |
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