Ricardo Ferraz1,2, Dário Silva3, Ana Rita Dias1,2, Vitorino Dias1, Miguel M Santos3, Luís Pinheiro3, Cristina Prudêncio1,4, João Paulo Noronha3, Željko Petrovski3, Luís C Branco3. 1. Ciências Químicas e das Biomoléculas (CQB) e Centro de Investigação em Saúde e Ambiente (CISA), Escola Superior de Saúde do Instituto Politécnico do Porto, 4400-330 Porto, Portugal. 2. LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal. 3. LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. 4. i3S, Instituto de Inovação e Investigação em Saúde, Universidade do Porto, 4099-002 Porto, Portugal.
Abstract
The preparation and characterization of ionic liquids and organic salts (OSILs) that contain anionic penicillin G [secoPen] and amoxicillin [seco-Amx] hydrolysate derivatives and their in vitro antibacterial activity against sensitive and resistant Escherichia coli and Staphylococcus aureus strains is reported. Eleven hydrolyzed β-lactam-OSILs were obtained after precipitation in moderate-to-high yields via the neutralization of the basic ammonia buffer of antibiotics with different cation hydroxide salts. The obtained minimum inhibitory concentration (MIC) data of the prepared compounds showed a relative decrease of the inhibitory concentrations (RDIC) in the order of 100 in the case of [C2OHMIM][seco-Pen] against sensitive S. aureus ATCC25923 and, most strikingly, higher than 1000 with [C16Pyr][seco-Amx] against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. These outstanding in vitro results showcase that a straightforward transformation of standard antibiotics into hydrolyzed organic salts can dramatically change the pharmaceutical activity of a drug, including giving rise to potent formulations of antibiotics against deadly bacteria strains.
The preparation and characterization of ionicn class="Chemical">liquids and organic salts (OSILs) that contain anionicpenicillin G [secoPen] and amoxicillin [seco-Amx] hydrolysate derivatives and their in vitro antibacterial activity against sensitive and resistant Escherichia coli and Staphylococcus aureus strains is reported. Eleven hydrolyzed β-lactam-OSILs were obtained after precipitation in moderate-to-high yields via the neutralization of the basic ammonia buffer of antibiotics with different cation hydroxidesalts. The obtained minimum inhibitory concentration (MIC) data of the prepared compounds showed a relative decrease of the inhibitory concentrations (RDIC) in the order of 100 in the case of [C2OHMIM][seco-Pen] against sensitive S. aureus ATCC25923 and, most strikingly, higher than 1000 with [C16Pyr][seco-Amx] against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. These outstanding in vitro results showcase that a straightforward transformation of standard antibiotics into hydrolyzed organic salts can dramatically change the pharmaceutical activity of a drug, including giving rise to potent formulations of antibiotics against deadly bacteria strains.
Entities:
Keywords:
active pharmaceutical ingredients-ionic liquids and organic salts (API-OSILs); penicillin G and amoxicillin hydrolysate derivatives; resistant bacteria; sensitive bacteria
Authors: Francisco Faísca; Vanessa Correia; Željko Petrovski; Luís C Branco; Helena Rebelo-de-Andrade; Miguel M Santos Journal: Pharmaceutics Date: 2022-04-17 Impact factor: 6.525
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