Synthesis and antibacterial activity of ionic liquids and organic salts based on penicillin g and amoxicillin hydrolysate derivatives against resistant bacteria

Fundacao para a Ciencia e Tecnologia through projects (PTDC/QUI-QOR/32406/2017, PEst-C/LA0006/2013) and PTDC/BTM-SAL/29786/2017, and one contract under Investigador FCT (L.C.B.). ZP thanks to Fundacao para a Ciencia e a Tecnologia, MCTES, for the Norma transitoria DL 57/2016 Program Contract. This work was also supported by the Associate Laboratory for Green Chemistry, which is financed by national funds from FCT/MEC, UIDB/50006/2020 and co‐financed by the ERDF under the PT2020 Partnership Agreement (POCI‐01‐ 0145‐FEDER‐007265). The authors also thank Solchemar company for support.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.publishersversionpublishe