A library of thirty two 3,4-diphenylfuranones related to both combretastatin A-4 and antifungal 5-(acyloxymethyl)-3-(halophenyl)-2,5-dihydrofuran-2-ones was prepared. Cytotoxic effects on a panel of cancer and normal cell lines and antiinfective activity were evaluated, and the data were complemented with tests for the activation of caspase 3 and 7. High cytotoxicity was observed in some of the halogenated analogues, eg. 3-(3,4-dichlorophenyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one with IC50 0.12-0.23 μM, but the compounds were also highly toxic against non-malignant control cells. More importantly, notable antibacterial activity indicating G+ selectivity has been found in the 3,4-diarylfuranone class of compounds for the first time. Hydroxymethylation of furanone C5 knocked out cytotoxic effects (up to 40 μM) while maintaining significant activity against Staphylococcus strains in some derivatives. MIC95 of the most promising compound, 3-(4-bromophenyl)-5,5-bis(hydroxymethyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one against S. aureus strain ATCC 6538 was 0.98 μM (0.38 μg/mL) and 3.9 μM (1.52 μg/mL) after 24 and 48 h, respectively.

CZ OPENSCREEN National Infrastructure for Chemical Biology Institute of Molecular Genetics Czech Academy of Sciences Vídeňská 1083 142 20 Praha 4 Czech Republic

Department of Biological and Medical Sciences Faculty of Pharmacy Charles University Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Bioorganic and Organic Chemistry Faculty of Pharmacy Charles University Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Medical Chemistry and Biochemistry Palacký University Hněvotínská 3 775 15 Olomouc Czech Republic

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