| Autor: |
Khabibrakhmanova AM; Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia., Faizova RG; Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia., Lodochnikova OA; Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia.; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia., Zamalieva RR; Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia., Latypova LZ; Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia., Trizna EY; Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia., Porfiryev AG; Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia., Tanaka K; Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako-shi 351-0198, Japan.; Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan., Sachenkov OA; N.I. Lobachevsky Institute of Mathematics and Mechanics, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia., Kayumov AR; Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia., Kurbangalieva AR; Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia. |
| Abstrakt: |
Over the past decades, 2(5 H )-furanone derivatives have been extensively studied because of their promising ability to prevent the biofilm formation by various pathogenic bacteria. Here, we report the synthesis of a series of optically active sulfur-containing 2(5 H )-furanone derivatives and characterize their biological activity. Novel thioethers were obtained by an interaction of stereochemically pure 5-( l )-menthyloxy- or 5-( l )-bornyloxy-2(5 H )-furanones with aromatic thiols under basic conditions. Subsequent thioethers oxidation by an excess of hydrogen peroxide in acetic acid resulted in the formation of the corresponding chiral 2(5 H )-furanone sulfones. The structure of synthesized compounds was confirmed by IR and NMR spectroscopy, HRMS, and single crystal X-ray diffraction. The leading compound, 26 , possessing the sulfonyl group and l -borneol moiety, exhibited the prominent activity against Staphylococcus aureus and Bacillus subtilis with MICs of 8 μg/mL. Furthermore, at concentrations of 0.4-0.5 μg/mL, the sulfone 26 increased two-fold the efficacy of aminoglycosides gentamicin and amikacin against S. aureus . The treatment of the model-infected skin wound in the rat with a combination of gentamicin and sulfone 26 speeded up the bacterial decontamination and improved the healing of the wound. The presented results provide valuable new insights into the chemistry of 2(5 H )-furanone derivatives and associated biological activities. |
