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

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

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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.

Original language	English
Article number	221
Journal	Pharmaceutics
Volume	12
Issue number	3
DOIs	https://doi.org/10.3390/pharmaceutics12030221
Publication status	Published - Mar 2020

Keywords

Active pharmaceutical ingredients-ionic liquids and organic salts (API-OSILs)
Penicillin G and amoxicillin hydrolysate derivatives
Resistant bacteria
Sensitive bacteria

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Ferraz, R., Silva, D., Dias, A. R., Dias, V., Santos, M. M., Pinheiro, L., Prudêncio, C., Noronha, J. P., Petrovski, Ž., & Branco, L. C. (2020). Synthesis and antibacterial activity of ionic liquids and organic salts based on penicillin g and amoxicillin hydrolysate derivatives against resistant bacteria. Pharmaceutics, 12(3), Article 221. https://doi.org/10.3390/pharmaceutics12030221

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

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",

author = "Ricardo Ferraz and D{\'a}rio Silva and Dias, {Ana Rita} and Vitorino Dias and Santos, {Miguel M.} and Lu{\'i}s Pinheiro and Cristina Prud{\^e}ncio and Noronha, {Jo{\~a}o Paulo} and {\v Z}eljko Petrovski and Branco, {Lu{\'i}s C.}",

note = "info:eu-repo/grantAgreement/FCT/3599-PPCDT/103664/PT# info:eu-repo/grantAgreement/FCT/5876/147218/PT# 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.",

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Ferraz, R, Silva, D, Dias, AR, Dias, V, Santos, MM , Pinheiro, L, Prudêncio, C, Noronha, JP , Petrovski, Ž & Branco, LC 2020, 'Synthesis and antibacterial activity of ionic liquids and organic salts based on penicillin g and amoxicillin hydrolysate derivatives against resistant bacteria', Pharmaceutics, vol. 12, no. 3, 221. https://doi.org/10.3390/pharmaceutics12030221

TY - JOUR

T1 - Synthesis and antibacterial activity of ionic liquids and organic salts based on penicillin g and amoxicillin hydrolysate derivatives against resistant bacteria

AU - Ferraz, Ricardo

AU - Silva, Dário

AU - Dias, Ana Rita

AU - Dias, Vitorino

AU - Santos, Miguel M.

AU - Pinheiro, Luís

AU - Prudêncio, Cristina

AU - Noronha, João Paulo

AU - Petrovski, Željko

AU - Branco, Luís C.

N1 - info:eu-repo/grantAgreement/FCT/3599-PPCDT/103664/PT# info:eu-repo/grantAgreement/FCT/5876/147218/PT# 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.

PY - 2020/3

Y1 - 2020/3

N2 - 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.

AB - 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.

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KW - Penicillin G and amoxicillin hydrolysate derivatives

KW - Resistant bacteria

KW - Sensitive bacteria

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U2 - 10.3390/pharmaceutics12030221

DO - 10.3390/pharmaceutics12030221

M3 - Article

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AN - SCOPUS:85081247754

SN - 1999-4923

VL - 12

JO - Pharmaceutics

JF - Pharmaceutics

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M1 - 221

ER -

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

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