title: Imidazoacridinone derivatives as efficient sensitizers in photoantimicrobial chemotherapy.
abstract: The objective of this study was to investigate a new potential photosensitizer (PS) in the photodynamic inactivation (PDI) of microorganisms in vitro (11 reference strains and 13 clinical isolates, representing common Gram-positive and Gram-negative human pathogens), with special emphasis on Candida albicans. We studied the light-induced cytotoxicity of the imidazoacridinone derivative C1330 toward fungal cells grown in planktonic form. We examined the influence of various parameters (time of incubation, PDI quencher effect, and C1330 accumulation in C. albicans cells) on the efficacy of light-dependent cytotoxicity. Additionally, we checked for the potential cyto- and phototoxic activity of C1330 against human dermal keratinocytes. In our research, we used a broadband incoherent blue light source (380 to 470 nm) with an output power of 100 mW/cm(2). In vitro studies showed that the C1330 action against C. albicans was a light-dependent process. C1330 was an efficient photosensitizer in the photodynamic inactivation of C. albicans, which reduced the growth of planktonic cells by 6.1 log10 units. Efficient accumulation of PS in the nucleus and vacuoles was observed after 30 min of incubation, which correlated with the highest photokilling efficacy. Significant changes in intracellular structure were observed upon illumination of C1330-incubated C. albicans cells. In the case of the human HaCaT cell line, approximately 40% of cells survived the treatment, which indicates the potential benefit of further study of the application of C1330 in photoantimicrobial chemotherapy. These data suggest that PDI may be a viable approach for the treatment of localized C. albicans infections.
authors.affiliation: Intercollegiate Faculty of Biotechnology, Laboratory of Molecular Diagnostics, University of Gdansk and Medical University of Gdansk, Gdansk, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Taraszkiewicz
authors.forename: Mariusz
authors.initials: M
authors.lastname: Grinholc
authors.forename: Krzysztof P
authors.initials: KP
authors.lastname: Bielawski
authors.forename: Anna
authors.initials: A
authors.lastname: Kawiak
authors.forename: Joanna
authors.initials: J
authors.lastname: Nakonieczna
mesh_terms: D000704:Analysis of Variance; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes; D008027:Light; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: C584011:C1330 compound; D006576:Heterocyclic Compounds, 4 or More Rings; D017319:Photosensitizing Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue
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