Interaction of the Antiarrhythmic Drug Procainamide with Phospholipid Bilayers

Suwalsky, Mario; Villena, Fernando Pardo-Manuel de; Bagnara, Margarita; Cp, Sotomayor

doi:10.1515/znc-1995-3-414

Cited by 3 publications

(1 citation statement)

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“…Since this estimation reflects the packing order of the acyl chain, the notion of anisotropy is also considered as an interpretation of membrane rigidity, in which a more rigid membrane displays a higher value of anisotropy. Laurdan is another fluorescent probe which is amphipathic in nature with a high sensitivity of excitation and emission spectra in terms of the physical state of the membrane332 . The fluorescent moiety of Laurdan probe lies within the shallow region of the bilayer, predominantly reporting the stiffening or dehydration of the lipid carbonyls333 (Fig.…”

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Novel D-LAK peptides combinations against mycobacteria : bioefficacy and mechanistic studies

Dede¹

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Emergence of multidrug-resistant tuberculosis (MDR-TB) renders the two most powerful and commonly used TB antibiotics, rifampicin and isoniazid, ineffective. There is an urgent need for the development of safe and effective strategies against drug-resistant TB. Based on previous studies, two novel antimicrobial peptides, namely D-LAK120-A and D-LAK120-HP13, both consist entirely of D-amino acid residues, have demonstrated inhibitory effect on MDR Mycobacterium tuberculosis (Mtb) strains when cultured in macrophages and potentiated the antimycobacterial activity of isoniazid in vitro. Here, the antimycobacterial activity of D-LAK peptides in combination with anti-TB drugs against MDR-TB clinical isolates was investigated. Furthermore, the mechanisms of action of the proline-containing and proline-free D-LAK peptides, anti-TB drugs alone or in combinations were studied using two mycobacterial models Mycobacterium smegmatis and the severely attenuated Mtb Bleupan. Finally, the applicability of these two microorganisms for mycobacterial studies was discussed. In vitro and ex vivo antimycobacterial assays revealed the synergy between D-LAK peptides and rifampicin or isoniazid against MDR Mtb strain. These findings suggested D-LAK peptide can facilitate the re-sensitization of MDR-TB clinical isolates towards rifampicin and isoniazid possibly through their surface activity. To gain further understanding on their mechanisms on mycobacteria, M. smegmatis was employed due to its fast-growing nature and widespread usage in TB studies. With confocal and transmission electron microscopy, the surface-active action of D-LAK peptides were observed which led to visible morphological changes in M. smegmatis. Using high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) metabolomics, trans-1,6-diphenyl-1,3,5hexatriene (DPH) and Laurdan fluorescence spectroscopy, it was shown that bacterial iv metabolism was substantially altered when challenged with anti-TB agents, specifically by the remodelling of mycobacterial membrane. The proline-containing D-LAK120-HP13 and proline-free D-LAK120-A peptides demonstrated disparate behaviours in the initiation of membrane remodelling which provides possible rationale for their synergistic interaction with anti-TB agents. These techniques were then applied to the study of another potential mycobacterial model Mtb Bleupan which was selected for its safer nature as a Mtb surrogate. Changes in membrane components triggered by anti-TB agents were observed but the effect was subtler than that observed in M. smegmatis. These findings suggested the potential of using these biophysical techniques to study the action of anti-TB drugs on mycobacteria and to elucidate the underlying mechanism of synergy demonstrated in the combinations of D-LAK peptides with anti-TB agents. Finally, the applicability of M. smegmatis and Mtb Bleupan to be exploited as a Mtb surrogate was evaluated. Some key differences in response to anti-TB agents were detected between Mtb Bleupan and M. smegmatis in...

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Novel D-LAK peptides combinations against mycobacteria : bioefficacy and mechanistic studies

Dede¹

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Interaction of dipyridamole derivatives with lipids in mixed floating Langmuir monolayers

Borissevitch¹,

Tabak²,

Borissevitch³

et al. 1996

Colloids and Surfaces B: Biointerfaces

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Interaction of Zn²⁺Ions with Phospholipid Multilayers

Suwalsky

Ungerer

Aguilar

et al. 1996

International Journal of Polymeric Materials

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Phospholipids are large natural amphipathic molecules which, in contact with water, assemble into higher molecular aggregates. The most relevant one is the bilayer for its relation to the structure, properties and functions of cell membranes. Given their structural complexity phospholipid bilayers are usually used as models for studying how biologically relevant chemicals affect the structure and functions of biomembranes. Zn is a trace element essential for the functional integrity of cell membranes. It is also a common contaminant of sea waters. Therefore, it was thought of interest to study the interaction of ZnZ+ ions with phospholipid bilayers in order to understand the way they interact with cell membranes. With this aim Zn2+, in a wide range of concentrations, was made to interact with multibilayers of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). This study was performed by X-ray diffraction. Besides, the interaction of Znz+ with DMPC liposomes was studied by fluorescence spectroscopy. The results showed that indeed Zn2+ interacted with both phospholipids. As its concentration increased it produced first a disorder effect which was reversed at higher concentrations.

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Interaction of the Antiarrhythmic Drug Procainamide with Phospholipid Bilayers

Cited by 3 publications

References 0 publications

Novel D-LAK peptides combinations against mycobacteria : bioefficacy and mechanistic studies

Novel D-LAK peptides combinations against mycobacteria : bioefficacy and mechanistic studies

Interaction of dipyridamole derivatives with lipids in mixed floating Langmuir monolayers

Interaction of Zn²⁺Ions with Phospholipid Multilayers

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Interaction of the Antiarrhythmic Drug Procainamide with Phospholipid Bilayers

Cited by 3 publications

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Novel D-LAK peptides combinations against mycobacteria : bioefficacy and mechanistic studies

Novel D-LAK peptides combinations against mycobacteria : bioefficacy and mechanistic studies

Interaction of dipyridamole derivatives with lipids in mixed floating Langmuir monolayers

Interaction of Zn2+Ions with Phospholipid Multilayers

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Interaction of Zn²⁺Ions with Phospholipid Multilayers