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Tackling bacterial resistance using antibiotics as ionic liquids and organic salts
Miguel M. Santos * 1 , Inês R. Grilo 2 , Ricardo Ferraz 3, 4 , Diogo A. Madeira 1 , Bárbara M. Soares 1, 2 , Núria Inácio 1, 2 , Luís Pinheiro 1 , Zeljko Petrovski 1 , Cristina Prudêncio 3, 5 , Rita G. Sobral 2 , Luís C. Branco 1
1  LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal
2  UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Caparica, Portugal
3  Ciências Químicas e das Biomoléculas (CQB) e Centro de Investigação em Saúde e Ambiente (CISA), Escola Superior de Saúde do Instituto Politécnico do Porto, Porto, Portugal
4  LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal
5  i3S, Instituto de Inovação e Investigação em Saúde, Universidade do Porto, Porto, Portugal

Published: 12 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5
10.3390/ECMC2019-06414
Abstract:

Bacterial resistance to current antibiotics has a major impact on worldwide human health, leading to 700K deaths every year. The development of novel antibiotics did not present significant progress, namely regarding clinical trials, over the last years due to low returns. Thus, innovative alternatives must be devised to tackle the continuous rise of antimicrobial resistance.

Ionic Liquids and Organic Salts from Active Pharmaceutical Ingredients (API-OSILs) have risen in academia for over 10 years as an efficient formulation for drugs with low bioavailability and permeability, as well as reduction or elimination of polymorphism, thereby potentially enhancing their pharmaceutical efficiency. To the best of our knowledge, our group is the first to perform research on the development of API-OSILs from antibiotics as a way to improve their efficiency. More specifically, we have successfully combined ampicillin, penicillin and amoxicillin as anions with biocompatible organic cations such as choline, alkylpyridiniums and alkylimidazoliums. Furthermore, we have also combined fluoroquinolones (ciprofloxacin and norfloxacin) as cations with biocompatible carboxylic and sulfonic acids.

In this communication, we present our latest developments in the synthesis and spectroscopic (NMR, FTIR) and physicochemical (DSC) characterization of ionic liquids and organic salts from these antibiotics, in addition to in vitro antimicrobial activity data, in particular towards Methicillin Resistant Staphylococcus aureus and multi-resistant Escherichia coli, as well as sensitive strains of gram-positive and gram-negative bacteria.

Keywords: Active Pharmaceutical Ingredients; API-OSILs; Antibiotics; Antimicrobial resistance; Ionic Liquids; Organic Salts; Polymorphism
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