Effect of the alkyl group in the piperazine N-substitution on the therapeutic action of rifamycins: A drug-membrane interaction study. (1st June 2018)

• Record Type: Journal Article
• Authors: Lage, Emílio V.; Magalhães, Joana; Pinheiro, Marina; Reis, Salette
• Is Part Of: Chemico-biological interactions. Volume 289(2018)
• Page Start: 75
• Page End: 80
• Publication Date: 2018-06-01
• Subjects: BAM -- Drug-membrane -- Membrane models -- Monolayers -- PM-IRRAS; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2018.04.027
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: In this work, we studied the effects of the N -alkyl group (methyl, cyclopentyl) in the piperazine ring of, respectively, rifampicin (RIF) and rifapentine (RPT) to correlate this substitution with their differential pharmacokinetic properties and overall clinical performance. Since this group is their only structural change, and given that they share the same pharmacological target, differences in their therapeutic behavior may respond to this asset, particularly in their interaction with lipid membranes across the organism. In this study, surface pressure-area isotherms, as well as spectroscopic and microscopic techniques of characterization of phospholipid monolayers at the air/water interface were used to gain insight into drug-membrane interactions. Differences in the affinity for lipid membranes for both drugs, given by the vibration frequency of characteristic chemical groups in the lipid, as well as by reflectivity and mean molecular area of the monolayer, seem to be due to the N -alkyl substituent and can contribute to provide a molecular explanation as why they pose different choices in the chemotherapy against the deadliest infectious disease, tuberculosis. Graphical abstract: Highlights: The effect of the alkyl group in the piperazine N -substitution on the therapeutic action of rifamycins was studied. Surface pressure-area isotherms, spectroscopic and microscopic techniques were used to study drug-membrane interactions. The interactions of Rifapentine with membranes are more pronounced than those of rifampicin.