Comparison of anti-Candida albicans activities of halogenomethylsulfonyl derivatives

Abstract

A rapidly growing resistance of Candida spp. requires a search for bioactive compounds with fungicidal or fungistatic activity. In this context a characteristics and comparison of antifungal properties of 19 sulfone derivatives were conducted. MICs of the Compounds were determined using the M27-A3 protocol following CLSI recommendations. The SAP expression was analyzed using RT-PCR; relative quantification was normalized against ACT1 in cells grown in YEPD and on Caco-2. 79 % of sulfone derivatives (15 out of 19) exhibited an activity against Candida albicans in the tested concentrations. While the addition of both chlorine and bromine atoms to halogenomethylsulfonyl groups stimulates sulfone's antifungal activity, a chlorine atom more effectively up-regulates antifungal properties of the tested sulfones. The insertion of a fluorine atom has a binary effect on antifungal properties of the tested sulfones. The fluorine atom enhances anti-Candida properties when introduced to the aromatic ring, while its presence in halogenomethylsulfonyl group generally lowers the Compound's efficiency. The deletion of particular SAP genes resulted in an increased susceptibility of C. albicans toward sulfones indicating the role of this gene family in resistance mechanisms. Furthermore, RT-PCR analysis demonstrated that sulfone derivatives inhibit the SAP2 expression but not that of SAP7.

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

“…In our study, novel compound 4 was shown to possess effective antifungal activity (MFC = 32–2 μg/mL) against the Candida reference strains and clinical isolates. Considering the structure-dependent effect, we propose that the presence of bromine and chlorine moiety attached to C 2 of phenyl ring in compound 4 may be the reason of its high antifungal activity (Bondaryk et al, 2015 ). As we showed previously, these elements are important for the interactions with fungal cells (Bondaryk et al, 2015 ; Staniszewska et al, 2015a , b ).…”

“…Considering the structure-dependent effect, we propose that the presence of bromine and chlorine moiety attached to C 2 of phenyl ring in compound 4 may be the reason of its high antifungal activity (Bondaryk et al, 2015 ). As we showed previously, these elements are important for the interactions with fungal cells (Bondaryk et al, 2015 ; Staniszewska et al, 2015a , b ). Indeed, bromodichloro- and dichloro-methyl substituents have a crucial role for reducing morphogenesis and adhesion of C. albicans without enhanced toxicity.…”

“…Moreover, structural analyses revealed that compound 4 -treated biofilms showed minor defects in the biofilm architecture (Figure 7 ). In our opinion, the reintroduction of fluorine atom instead of chlorine at the C 4 position of the benzene ring can exert activity against Candida sessile cells (Bondaryk et al, 2015 ; Staniszewska et al, 2015a , b ). Candida albicans biofilm heterogeneity has a direct impact on antifungal sensitivity to compound 4 , based on our in vitro study.…”

“…Candida albicans is polymorphic fungus with the ability to form yeast and hyphal cells, both critical for biofilm development and maintenance (Gulati and Nobile, 2016 ). Our recent studies (Bondaryk et al, 2015 ; Staniszewska et al, 2015a , b ) demonstrated that inhibition of hyphal growth attenuated virulence in an in vitro model of superficial candidiasis, and a disruption of this cellular process might serve as an effective therapeutic intervention. Thus, inhibition of dimorphism may provide an alternative approach allowing finding compounds with the potential to control C. albicans infections (Lu et al, 2014 ).…”