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Candida albicansrepresents an interesting microorganism to study complex host-pathogen interactions and for the development of effective antifungals. Our goal was to assess the efficacy of 4-chloro-3-nitrophenyldifluoroiodomethyl sulfone (named Sulfone) against the C. albicansinfections in the Galleria mellonellahost model. We assessed invasiveness of CAI4 parental strain and mutants: kex2Δ/KEX2and kex2Δ/kex2Δ in G. mellonellatreated with Sulfone. We determined that KEX2expression was altered following Sulfone treatment in G. mellonella-C. albicansinfection model. Infection with kex2Δ/kex2Δinduced decreased inflammation and minimal fault in fitness of larvae vs CAI4. Fifty percent of larvae died within 4–5 days (Pvalue < 0.0001) when infected with CAI4 and kex2Δ/KEX2at 109CFU/mL; survival reached 100% in those injected with kex2Δ/kex2Δ. Larvae treated with Sulfone at 0.01 mg/kg 30 min before infection with all C. albicanstested survived infection at 90–100% vs C. albicansinfected-PBS-treated larvae. Hypersensitive to Sulfone, kex2Δ/kex2Δreduced virulence in survival. KEX2was down-regulated when larvae were treated with Sulfone: 30 min before and 2 h post-SC5314-wild-type infection respectively. kex2Δ/kex2Δwas able to infect larvae, but failed to kill host when treated with Sulfone. Sulfone can be used to prevent or treat candidiasis. G. mellonellafacilitates studding of host-pathogen interactions, i.e., testing host vs panel of C. albicansmutants when antifungal is dosed.

Aim:The effect of KEX2mutations on C. albicansvirulence and resistance to halogenated methyl sulfones was assessed. Materials & methods:The mechanism of action of sulfones was studied using flow cytometry and microscopy. Expression of KEX2and SAP5was assessed using quantitative Real-Time-PCR. 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide and lactate dehydrogenase assays were elaborated to study, respectively, metabolism of Candidatreated with sulfones and their cytotoxicity against tissues. Inflammatory response was detected by ELISA. Results:Lysosome permeabilization and dose-dependent programmed cell death under sulfones were noted. KEX2induction depended on halogenomethylsulfonyl groups, which affected cell wall biosynthesis and adhesion. Conclusion:Sulfones treatment reduced Candidapathogenicity in Galleria mellonella. Sulfones are an alternative for antifungal therapies due to their safety profile and antibiofilm activity.

Hydrolytic enzymes e.g., Saps and KEX2are, due to their role in Candidavirulence, considered important targets for new synthetic inhibitors. MICTIand MICPIvalues indicate that disruption of SAP1-3significantly increases the resistance of Candidamutants to β-ketosulfone (1). Contrariwise, sap123∆showed sensitive phenotype to halogenated methylphenyl sulfone (2). Anticandidal potency of 2differed in the Candidacells of kex2∆. Sulfone is the most effective agent against the Candida albicans kex2∆double mutant (MICTIof 0.5 μg mL–1). Up-regulation of KEX2mediated the resistance of sap4-6∆towards 2. Both sulfones tested reduced the adhesion of the wild type cells significantly (P< 0.05). Contrariwise, sap123∆showed significantly enhanced adhesion capability when 1was used (P< 0.05). Both sulfones had weak fungicidal effect on mature C albicansbiofilms. It was shown that the uptake of IP correlates with the membrane perturbations caused by 1 in the blastoconidial cells. Sulfones were found to disturb the basic developmental phases of biofilm growth: adhesion and morphogenesis. Altered KEX2levels for 1can be caused by the compensatory mechanism for the maintenance of cell wall integrity and morphogenesis. KEX2decreases the antifungal activity of sulfones. Sulfones affecting the crucial virulence factors of Candidacan even eliminate these fungal infections.

Hydrolytic enzymes e.g., Saps and Kex2 are, due to their role in Candidavirulence, considered important targets for new synthetic inhibitors. MICTI and MICPI values indicate that disruption of SAP1-3significantly increases the resistance of Candida mutants to β-ketosulfone (1). Contrariwise, sap123Δshowed sensitive phenotype to halogenated methylphenyl sulfone (2). Anticandidal potency of 2 differed in the Candida cells of kex2Δ. Sulfone is the most effective agent against the Candida albicans kex2Δdouble mutant (MICTI of 0.5 µg mL−1). Up-regulation of KEX2mediated the resistance of sap4-6Δtowards 2. Both sulfones tested reduced the adhesion of the wild type cells significantly (P≤ 0.05). Contrariwise, sap123Δshowed significantly enhanced adhesion capability when 1 was used (P≤ 0.05). Both sulfones had weak fungicidal effect on mature C. albicansbiofilms. It was shown that the uptake of IP correlates with the membrane perturbations caused by 1 in the blastoconidial cells. Sulfones were found to disturb the basic developmental phases of biofilm growth: adhesion and morphogenesis. Altered KEX2levels for 1 can be caused by the compensatory mechanism for the maintenance of cell wall integrity and morphogenesis. KEX2decreases the antifungal activity of sulfones. Sulfones affecting the crucial virulence factors of Candidacan even eliminate these fungal infections.

Aryl halomethyl sulfones are halogenated organosulfur compounds which continuously draw attention owing to their bioactivity as well as wide applications in organic synthesis. This review summarizes the methods for their preparation, describing the reported routes to fluoro, chloro, bromo and iodo derivatives. Their synthetic and biological applications are also highlighted.

A series of 5-halogenomethylsulfonylbenzimidazole and benzotriazole derivatives was synthesized as potential antibacterial agents. A new method of synthesis of benzimidazoles was developed. The antimicrobial activities of these compounds were tested against a series of reference and clinical strains. The reference strains include Gram-positive bacteria (S. aureus, S. epidermidis, B. subtilis, B. cereus, E. hirae, M. luteus) and Gram-negative rods (E. coli, P. vulgaris, P. aeruginosa, B. bronchiseptica). The clinical strains include six methicillin-resistant (MRSA) and two methicillin-sensitive (MSSA) S. aureus strains, one methicillin-resistant S. epidermidis, three E. faecalis and two E. faecium strains. Compound with trifluoromethyl- substituent at C-2 position (4) displayed significant antibacterial activities comparable with nitrofurantoin against four strains, and higher against Micrococcus luteus. MIC values for clinical Staphylococci strains (MRSA) were 12.5-25 μg/mL; for Enterococcus strains these values were 50-100 μg/mL. MIC values for reference and clinical strains of Staphylococcus and Enterococcus group were similar, respectively.

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The treatment of 2-(methylthio)ethanol (methioH) with two equivalents of Me2Zn in CH2Cl2 affords a tetranuclear aggregate with two monomeric MeZn(methio) units joined by two MeZnCl moieties. This result demonstrates that transfer of a chloride ion to Zn takes place on the addition of a donor-functionalized alcohol to Me2Zn in CH2Cl2 solution. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Upon replacement of the ester functionality by ketone functionality in α-hydroxy carbonyl compounds dramatic structural changes of donor-functionalized alkoxides of aluminium are observed: complete reversal of the stereochemistry of the aluminium alkoxide adduct formation, dissociation of the five-coordinate dimer to a monomeric four-coordinate chelate complex; the first example of an aluminium Cram-type chelate complex derived from the reaction of Et3Al with an equimolar amount of rac-acetoin is reported.

A series of compounds (III) (16 examples) is synthesized without the use of any toxic solvent via a simple procedure which also includes an easy work‐up.