Passive Diffusion of Ciprofloxacin and its Metalloantibiotic: A Computational and Experimental study

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Sousa, CF (Author) Other; Coimbra, JTS (Author) Other; Ferreira, M (Author) Other; Pereira Leite, C (Author) Other; Salette Reis (Author) FFUP; Ramos, MJ (Author) FCUP; Pedro A Fernandes (Author) FCUP; Paula Gameiro (Author) FCUP

Journal

Title: Journal of Molecular Biology

Vol. 433

ISSN: 0022-2836

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 6 Citations

Scopus - 6 Citations

Other information

Authenticus ID: P-00T-NCM

DOI: 10.1016/j.jmb.2021.166911

Abstract (EN): Fluoroquinolones (FQ) are antibiotics widely used in clinical practise, but the development of bacterial resistance to these drugs is currently a critical public health problem. In this context, ternary copper complexes of FQ (CuFQPhen) have been studied as a potential alternative. In this study, we compared the passive diffusion across the lipid bilayer of one of the most used FQ, ciprofloxacin (Cpx), and its ternary copper complex, CuCpxPhen, that has shown previous promising results regarding antibacterial activity and membrane partition. A combination of spectroscopic studies and molecular dynamics simulations were used and two different model membranes tested: one composed of anionic phospholipids, and the other composed of zwitterionic phospholipids. The obtained results showed a significantly higher membrane permeabilization activity, larger partition, and a more favourable free energy landscape for the permeation of CuCpxPhen across the membrane, when compared to Cpx. Furthermore, the computational results indicated a more favourable translocation of CuCpxPhen across the anionic membrane, when compared to the zwitterionic one, suggesting a higher specificity towards the former. These findings are important to decipher the influx mechanism of CuFQPhen in bacterial cells, which is crucial for the ultimate use of CuFQPhen complexes as an alternative to FQ to tackle multidrug-resistant bacteria.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17