AUTHOR=Staniszewska Monika , Bondaryk Małgorzata , Wieczorek Magdalena , Estrada-Mata Eine , Mora-Montes Héctor M. , Ochal Zbigniew 

TITLE=Antifungal Effect of Novel 2-Bromo-2-Chloro-2-(4-Chlorophenylsulfonyl)-1-Phenylethanone against Candida Strains

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01309

DOI=10.3389/fmicb.2016.01309

ISSN=1664-302X

ABSTRACT=<p>We investigated the antifungal activity of novel a 2-bromo-2-chloro-2-(4-chlorophenylsulfonyl)-1-phenylethanone (compound <bold>4</bold>). The synthesis of compound <bold>4</bold> was commenced from sodium 4-chlorobenzene sulfinate and the final product was obtained by treatment of α-chloro-β-keto-sulfone with sodium hypobromite. The sensitivity of 63 clinical isolates belonging to the most relevant <italic>Candida</italic> species toward compound <bold>4</bold> using the method M27-A3 was evaluated. We observed among most of the clinical strains of <italic>C. albicans</italic> MIC ranging from 0.00195 to 0.0078 μg/mL. Compound <bold>4</bold> at 32 μg/mL exhibited fungicidal activity against nine <italic>Candida</italic> strains tested using the MFC assay. Compound <bold>4</bold> displayed anti-<italic>Candida</italic> activity (with clear endpoint) against 22% of clinical strains of <italic>Candida</italic>. Under compound <bold>4</bold>, <italic>Candida</italic> susceptibility and tolerance, namely paradoxical effect (PG), was found for only two clinical isolates (<italic>C. glabrata</italic> and <italic>C. parapsilosis</italic>) and reference strain 14053 using both M27-A3 and MFC method. We found that compound <bold>4</bold> does not induce toxicity <italic>in vivo</italic> against larvae of <italic>Galleria mellonella</italic> (≥97% survival) and it displays reduced toxicity on mammalian cells <italic>in vitro</italic> (&lt; CC<sub>20</sub> at 64 μg/mL). Furthermore, XTT assay denoted clear metabolic activity of sessile cells in the presence of compound <bold>4</bold>. Thus, the effect of compound <bold>4</bold> on formed <italic>C. albicans</italic> biofilms was minimal. Moreover, strain 90028 exhibited no defects in hyphal growth on Caco-2 monolayer under compound <bold>4</bold> influence at MIC = 16 μg/mL. The MIC values of compound <bold>4</bold> against <italic>C. albicans</italic> 90028, in medium with sorbitol did not suggest that compound <bold>4</bold> acts by inhibiting fungal cell wall synthesis. Our findings with compound <bold>4</bold> suggest a general strategy for antifungal agent development that might be useful in limiting the emergence of resistance in <italic>Candida</italic> strains.</p>