The influence of functional groups on the permeation and distribution of antimycobacterial rhodamine chelators

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Moniz, T (Author) Other; Leite, A (Author) Other; Silva, T (Author) Other; Paula Gameiro (Author) FCUP; Gomes, MS (Author) Other; de Castro, B (Author) FCUP; Maria Rangel (Author) ICBAS

Journal

Title: Journal of Inorganic Biochemistry

Vol. 175

Pages: 138-147

ISSN: 0162-0134

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-00N-2W0

DOI: 10.1016/j.jinorgbio.2017.07.017

Abstract (EN): We formerly hypothesized a mechanism whereby the antimycobacterial efficiency of a set of rhodamine labelled iron chelators is improved via the rhodamine fluorophore which enhances the chelators' permeation properties through membranes. To validate our hypothesis in a cellular context and to understand the influence of the structure of the fluorophore on the chelator's uptake and distribution within macrophages we now report comparative confocal microscopy studies performed with a set of rhodamine labelled chelators. We identify the functional groups of the chelator's framework that favor uptake by macrophages and conclude that the antimycobacterial effect is strongly related with the capacity of the chelator to distribute within the host cell and its compartments, a property that is closely related with the chelators' ability to interact with membranes. The quantification of the chelators' interaction with membranes was assessed through measurement of the corresponding partition constants in liposomes. The overall results support that the compounds which are preferentially taken up are the most efficient antimycobacterial chelators and for that reason we infer that the biological activity is modulated by the structural features of the fluorophore.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10