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"Clicking" an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability.

ABSTRACT: A covalent conjugate between an antibacterial ionic liquid and an antimicrobial peptide was produced via "click" chemistry, and found to retain the parent peptide's activity against multidrug-resistant clinical isolates of Gram-negative bacteria, and antibiofilm action on a resistant clinical isolate of Klebsiella pneumoniae, while exhibiting much improved stability towards tyrosinase-mediated modifications. This unprecedented communication is a prelude for the promise held by ionic liquids -based approaches as tools to improve the action of bioactive peptides.

SUBMITTER: Gomes A

PROVIDER: S-EPMC7504088 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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"Clicking" an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability.

Gomes Ana A Bessa Lucinda J LJ Correia Patrícia P Fernandes Iva I Ferraz Ricardo R Gameiro Paula P Teixeira Cátia C Gomes Paula P

International journal of molecular sciences 20200826 17

A covalent conjugate between an antibacterial ionic liquid and an antimicrobial peptide was produced via "click" chemistry, and found to retain the parent peptide's activity against multidrug-resistant clinical isolates of Gram-negative bacteria, and antibiofilm action on a resistant clinical isolate of <i>Klebsiella pneumoniae</i>, while exhibiting much improved stability towards tyrosinase-mediated modifications. This unprecedented communication is a prelude for the promise held by ionic liqui ...[more]

PMID: 32859111

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Project description:IntroductionCancer is a big challenge of the 21 century, whose defeat requires efficient antitumor drugs.ObjectivesThe paper aims to investigate the synergistic effect of two structural building blocks, phenothiazine and poly(ethylene glycol), towards efficient antitumor drugs.MethodsTwo PEGylated phenothiazine derivatives were synthetized by attaching poly(ethylene glycol) of 550 Da to the nitrogen atom of phenothiazine by ether or ester linkage. Their antitumor activity has been investigated on five human tumour lines and a mouse tumor line as well, by determination of IC50. The in vivo toxicity was determined by measuring the LD50 in BALB/c mice by the sequential method and the in vivo antitumor potential was measured by the tumours growth test. The antitumor mechanism was investigated by complexation studies of zinc and magnesium ions characteristic to the farnesyltransferase enzyme, by studies of self-aggregation in the cells proximity and by investigation of the antitumor properties of the acid species resulted by enzymatic cleavage of the PEGylated derivatives.ResultsThe two compounds showed antitumor activity, with IC50 against mouse colon carcinoma cell line comparable with that of the traditional antitumor drugs 5-Fluorouracil and doxorubicin. The phenothiazine PEGylation resulted in a significant toxicity diminishing, the LD50 in BALB/c mice increasing from 952.38 up to 1450 mg/kg, in phenothiazine equivalents. Both compounds inflicted a 92% inhibition of the tumour growth for doses much smaller than LD50. The investigation of the possible tumour inhibition mechanism suggested the nanoaggregate formation and the cleavage of ester bonds as key factors for the inhibition of cancer cell proliferation and biocompatibility improvement.ConclusionPhenothiazine and PEG building blocks have a synergetic effect working for both tumour growth inhibition and biocompatibility improvement. All these findings recommend the PEGylated phenothiazine derivatives as a valuable workbench for a next generation of antitumor drugs.

Dataset Information

"Clicking" an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability.

Publications

"Clicking" an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability.

Similar Datasets

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