Synthesis and Antibacterial Activity of Ionic Liquids and Organic Salts Based on Penicillin G and Amoxicillin hydrolysate Derivatives against Resistant Bacteria

Ricardo Ferraz; Dário Silva; Ana Rita Dias; Vitorino Dias; Miguel M Santos; Luís Pinheiro; Cristina Prudêncio; João Paulo Noronha; Željko Petrovski; Luís C Branco

doi:10.3390/pharmaceutics12030221

Synthesis and Antibacterial Activity of Ionic Liquids and Organic Salts Based on Penicillin G and Amoxicillin hydrolysate Derivatives against Resistant Bacteria

Pharmaceutics. 2020 Mar 2;12(3):221. doi: 10.3390/pharmaceutics12030221.

Authors

Affiliations

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.

Keywords: active pharmaceutical ingredients-ionic liquids and organic salts (API-OSILs); penicillin G and amoxicillin hydrolysate derivatives; resistant bacteria; sensitive bacteria.