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

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 ß-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.This research was funded by by Fundação para a Ciência e Tecnologia through projects (PTDC/QUI-QOR/32406/2017, PEst-C/LA0006/2013, PTDC/CTM/103664/2008) and PTDC/BTM- SAL/29786/2017, and one contract under Investigador FCT (L.C.B.). ZP thanks to Fundacão para a Ciência e a Tecnologia, MCTES, for the Norma transitória 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 (UID/QUI/50006/2013), 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