61496-44-4Relevant academic research and scientific papers
New synthetic sulfone derivatives inhibit growth, adhesion and the leucine arylamidase APE2 gene expression of Candida albicans in vitro
Staniszewska, Monika,Bondaryk, Ma?gorzata,Ochal, Zbigniew
, p. 314 - 321 (2015/03/04)
The successful preventing and effective treatment of invasive Candida albicans infections required research focused on synthesis of new classes of agents and antifungal activity studies. Bromodichloromethyl-4-chloro-3-nitrophenyl sulfone (named compound 6); dichloromethyl-4-chloro-3-nitrophenyl sulfone (named 7); and chlorodibromomethyl-4-hydrazino-3-nitrophenyl sulfone (named 11) on inhibition of planktonic cells' growth, leucine arylamidase APE2 gene expression, and adhesion to epithelial cells were investigated. In vitro anti-Candida activities were determined against wild-types, and the morphogenesis mutants: Δefg1 and Δcph1. MICs of compounds 6, 7 and 11 (concentrated at 0.25-16 μg/ml) were determined using the Clinical and Laboratory Standards Institute Broth Microdilution Method (M27-A3 Document). APE2 expression was analyzed using RT-PCR; relative quantification was normalized against ACT1 in cells growth in YEPD and on Caco-2 cell line. Adherence assay of C. albicans to Caco-2 was performed in 24-well-plate. The structure activity relationship suggested that sulfone containing hydrazine function at C-1 (compound 11) showed higher antifungal activity (cell inhibition% = 100 at 1-16 μg/ml) than the remaining sulfones with chlorine at C-1. Δcph1/Δefg1 was highly sensitive to compound 11, while the sensitivity was reduced in Δcph1/Δefg1::EFG1 (% = 100 at 16-fold higher concentration). Compound 11 significantly affected adherence to epithelium (P ≤0.05) and hyphae formation. The APE2 up-regulation plays role in sulfones' resistance on MAP kinase pathway. Either CPH1 or EFG1 play a role in the resistance mechanism in sulfones. The strain-dependent phenomenon is a factor in the sulfone resistance mechanism. Sulfones' mode of action was attributed to reduced virulence arsenal in terms of adhesiveness and pathogenic potential related to the APE2 expression and morphogenesis.
Synthesis and in vitro antibacterial activity of 5-halogenomethylsulfonyl- benzimidazole and benzotriazole derivatives
Ochal, Zbigniew,Bretner, Maria,Wolinowska, Renata,Tyski, Stefan
, p. 1129 - 1136 (2014/01/06)
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.
