Santos, Miguel

NOVA University Lisbon (Portugal)

Miguel Santos received his PhD degree in Chemistry in 2013 by the University of Aveiro. His thesis focused on the supramolecular recognition of organic and inorganic anions by azacalix[2]arene[2]triazine macrocycles and isoftalamides. He is currently a Researcher at the Cultural Heritage and Responsive Materials Group from LAQV-REQUIMTE focusing on the development of Organic Salts and Ionic Liquids from Active Pharmaceutical Ingredients as highly effective ionic formulations of commercial drugs.


Enhanced formulations of Hydroxychloroquine as Organic Salts and Ionic Liquids to fight COVID-19


Since the beginning of the COVID-19 pandemic, SARS-CoV-2 has infected more than 134 million people worldwide, from which 2.9 million have died. Multiple advances in the pharmacological treatment of severe cases have been made over the last year such as dexamethasone to control inflammatory response and repurposed drugs such as hydroxychloroquine (HCQ) and remdesivir as antivirals. However, HCQ, and despite showing efficacy against SARS-CoV-2 by putatively increasing lysosomal pH, it is no longer recommended for treatment of severe COVID-19 due to its toxicity at the required therapeutic doses. Nonetheless, it has shown to be an effective alternative in avoiding complications in milder cases, especially in a combinatorial regime. Still there is a need for the development of more effective antiviral drugs against SARS-CoV-2, but a very long journey is expected in the search of novel drugs. A promising alternative is the enhancement of current drugs by associating them with chemical adjuvants. For more than a decade, the combination of Active Pharmaceutical Ingredients (APIs) with such adjuvants as Organic Salts and Ionic Liquids (OSILs) has risen in the academia, and has recently reached Pharma, as an alternative to improve the properties of current drugs, in particular bioavailability, chemical and thermal stability, safety and therapeutic efficiency. In our lab, several antibiotics (β-lactam, fluoroquinolones) and bone anti-resorbing agents (bisphosphonates), among others, have been successfully combined as anions and/or cations with biocompatible organic counter-ions, with very interesting chemical and biological improvements being observed. Most recently, we set out to explore the benefits of the OSILs approach with hydroxychloroquine (HCQ-OSILs) as effective antivirals against SARS-CoV-2. Hence, in this communication we present the synthesis and characterization of fourteen novel mono- and dicationic HCQ-OSILs, and also a comparison of their water solubility and octanol-water partition coefficients with HCQ sulfate. Moreover, in vitro cytotoxicity data on Vero E6 cells and antiviral activity profile against the SARS- CoV-2 virus of the prepared HCQ-OSILs will be rationalized and discussed. Acknowledgments This work was supported by FCT-MCTES (Research 4 COVID-19 nº 582, PTDC/QUIQOR/32406/2017, PEst-C/LA0006/2013, RECI/BBBBQB/0230/2012) and by the Associate Laboratory for Green Chemistry – LAQV (FCT-MCTES UIDB/50006/2020).

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