In vitro viral photostimulated inactivation by a synthetic halogenated anthraquinone

MUGAS ML; KONIGHEIM BS; ROUMANA A; AGUILAR JJ; CONTIGIANI MS; FOUSTERIS M; NÚÑEZ MONTOYA SC

Tampa Florida

Encuentro; 2018 BIENNIAL MEETING AMERICAN SOCIETY FOR PHOTOBIOLOGY; 2018

AMERICAN SOCIETY FOR PHOTOBIOLOGY

Anthraquinones (AQs) are an important class of natural compounds; some of them have showed antimicrobial activity that can be increased by light. Several synthetic pathways have been developed to obtain them. Since the introduction of a halogen atom has been widely adopted as a strategy for the development of highly effective photosensitizers, the aim of this work was to obtain a synthetic halogenated AQ and study its photostimulated ability to the viral inactivation on infected cells.Friedel-Crafts acylation of resorcinol with 4-bromophthalic anhydride afforded a synthetic brominated AQ that was identified by NMR spectroscopy and HPLC-DAD-ESI-QTOF analysis. Cytotoxicity on host cells (Vero cells) and viral inactivation (Herpes Simplex virus Type 1, HSV-1, KOS strain) were determined by means of the observation of the cytopathic effect (Optical microscopy) and evaluation of cellular viability (CV, uptake test of Neutral Red). Infected cells with HSV-1, were treated with AQ at Maximum Non-Cytotoxic Concentration (MNCC), and then were submitted under two experimental conditions: darkness and irradiation (actinic lamp) dose = 0.59 Jcm-2. Active viral particles were detected by extraction of cellular content and its subsequent inoculation in a new cell monolayer.6-bromo-xantopurpurin (6-BrX) was obtained as one of reaction products (yield = 1.27 %, purity = 91.9 %). In darkness, 6-BrX was not able to inactivate the extracellular virus, but a low inactivation of the intra cellular virus (28.3 %) was observed. Under irradiation, 72.6 % of extracellular virus and 83.3 % of intra cellular virus were inactivated by a 6-BrX photosensibilization process. Cytotoxicity test showed that the combination of 6-BrX (MNCC = 10 µM) with irradiation did not reduce the viability of the host cells (% CV = 97.1). In conclusion, 6-BrX has shown to be photoactive and able to inactivate HSV-1 in vitro by photostimulation without a deleterious effect on host cells.