Cationic amphiphilic Zn-porphyrin with high antifungal photodynamic potency.
Abstract
Photodynamic therapy (PDT) is a promising alternative approach particularly attractive
for treatment of localized fungal infections. It is based on compounds, photosensitizers
(PSs), which when excited with visible light, generate reactive species that ultimately
cause cell death. Such species have short lifespans; as a consequence, efficiency
and selectivity of the PDT treatment depend mainly on the properties of the PSs. This
study is the first to explore the effect of cationic porphyrin-based photosensitizers
on Saccharomyces cerevisiae, a member of the fungus kingdom. The study investigates
which properties of the PS are essential for efficient antifungal PDT. Cationic Zn(ii)
meso-tetrakis(N-alkylpyridinium-2-yl)porphyrins (ZnP) with identical tetrapyrrole
core and photo-physical properties, but with different substituents at the meso positions
of the porphyrin ring were studied. Attaching six-carbon aliphatic chains to the four
pyridyl nitrogens at all meso positions to the porphyrin ring produced a highly photo-efficient
amphiphilic, water soluble PS, with minimal dark toxicity. It was taken up by the
yeast cells and upon illumination suppressed metabolism by inactivating cytoplasmic
and mitochondrial enzymes, and compromising plasma membrane barrier function. At low
concentrations (up to 5 μM) the tetrahexyl derivative was a much more powerful antifungal
agent than the commercially available chlorin e6. The more lipophilic tetraoctyl analog
was also highly photo-efficient but displayed strong dark toxicity, presumably due
to higher lipophilicity which might affect the lipid bilayer of membranes. Results
presented here can assist the design of antifungal agents whose biological action
depends on efficient and rapid uptake by the cells.
Type
Journal articleSubject
Saccharomyces cerevisiaeCations
Zinc
Metalloporphyrins
Photosensitizing Agents
Antifungal Agents
Surface-Active Agents
Photochemotherapy
Microbial Sensitivity Tests
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https://hdl.handle.net/10161/24999Published Version (Please cite this version)
10.1039/c7pp00143fPublication Info
Moghnie, Sara; Tovmasyan, Artak; Craik, James; Batinic-Haberle, Ines; & Benov, Ludmil (2017). Cationic amphiphilic Zn-porphyrin with high antifungal photodynamic potency. Photochemical & photobiological sciences : Official journal of the European Photochemistry
Association and the European Society for Photobiology, 16(11). pp. 1709-1716. 10.1039/c7pp00143f. Retrieved from https://hdl.handle.net/10161/24999.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Ines Batinic-Haberle
Professor Emeritus of Radiation Oncology
A major interest of mine has been in the design and synthesis of Mn porphyrin(MnP)-based
powerful catalytic antioxidants which helped establish structure-activity relationship
(SAR). It relates the redox property of metalloporphyrins to their ability to remove
superoxide. SAR has facilitated the design of redox-active therapeutics and served
as a tool for mechanistic considerations. Importantly SAR parallels the magnitu

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