Antimicrobial activity of N-acylphenothiazines and their influence on lipid model membranes and erythrocyte membranes

Noboru Motohashi, Masami Kawase, J. Molnár, L. Ferenczy, Olga Wesolowska, Andrzej B. Hendrich, Malgorzata Bobrowska-Hägerstrand, Henry Hägerstrand, Krystyna Michalak

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The antibacterial activity and influence on lipid model membranes and erythrocyte membranes of 24 N-acylphenothiazines and trifluoperazine were studied. (1) Among 24 phenothiazines, the antimicrobial activity of amino maleates was the highest. (2) The influence of phenothiazines on model liposome and erythrocyte membranes was studied using N-phenyl-1naphthylamine (NPN) as fluorescence probe. From the three types of phenothiazine substitution (H, CI, CF3) at position 2, CF3-phenothiazines were the most effective in the interaction with liposomal membranes. (3) As measured by the polarization degree of 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence, the alteration of membrane fluidity induced by CF3-phenothiazines was the biggest. Surprisingly, phenothiazines induced stomatocytic shape alterations (invaginations) in erythrocytes and at higher concentrations, also hemolysis of erythrocytes was observed. (4) The microcalorimetic measurements of influence of phenothiazines on thermal behaviour of synthetic lipid systems confirmed the previously obtained results. The main transition temperature and enthalpy of transition of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were significantly modified by CF3-phenothiazines, suggesting their penetration of the lipid bilayer. Above results show that phenothiazine maleates were generally more effective than other phenothiazines used in this study.

Original languageEnglish
Pages (from-to)590-599
Number of pages10
JournalArzneimittel-Forschung
Volume53
Issue number8
Publication statusPublished - 2003

Fingerprint

Phenothiazines
Erythrocyte Membrane
Membrane Lipids
Membranes
Lipids
Maleates
Erythrocytes
Fluorescence
Diphenylhexatriene
Trifluoperazine
Membrane Fluidity
Lipid bilayers
acylphenothiazine
Fluidity
Transition Temperature
Lipid Bilayers
Hemolysis
Phosphatidylcholines
Liposomes
Enthalpy

Keywords

  • N-Acylphenothiazines, anti-microbioal activity, erythrocyte membrane, lipid model membrane, liposome

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Pharmacology

Cite this

Antimicrobial activity of N-acylphenothiazines and their influence on lipid model membranes and erythrocyte membranes. / Motohashi, Noboru; Kawase, Masami; Molnár, J.; Ferenczy, L.; Wesolowska, Olga; Hendrich, Andrzej B.; Bobrowska-Hägerstrand, Malgorzata; Hägerstrand, Henry; Michalak, Krystyna.

In: Arzneimittel-Forschung, Vol. 53, No. 8, 2003, p. 590-599.

Research output: Contribution to journalArticle

Motohashi, N, Kawase, M, Molnár, J, Ferenczy, L, Wesolowska, O, Hendrich, AB, Bobrowska-Hägerstrand, M, Hägerstrand, H & Michalak, K 2003, 'Antimicrobial activity of N-acylphenothiazines and their influence on lipid model membranes and erythrocyte membranes', Arzneimittel-Forschung, vol. 53, no. 8, pp. 590-599.
Motohashi, Noboru ; Kawase, Masami ; Molnár, J. ; Ferenczy, L. ; Wesolowska, Olga ; Hendrich, Andrzej B. ; Bobrowska-Hägerstrand, Malgorzata ; Hägerstrand, Henry ; Michalak, Krystyna. / Antimicrobial activity of N-acylphenothiazines and their influence on lipid model membranes and erythrocyte membranes. In: Arzneimittel-Forschung. 2003 ; Vol. 53, No. 8. pp. 590-599.
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