We have designed, synthesized, and evaluated 5-benzylidene-rhodanine- and 5-benzylidenethiazolidine-2,4-dione-based compounds as inhibitors of bacterial enzyme MurD with E. coli IC50 in the range 45-206 µM. The high-resolution crystal structure of MurD in complex with (R,Z)-2-(3-[{4-([2,4-dioxothiazolidin-5-ylidene]methyl)phenylamino}methyl)benzamido)pentanedioic acid revealed details of the binding mode of the inhibitor within the active site and provides a good foundation for structure-based design of a novel generation of MurD inhibitors.
COBISS.SI-ID: 2876529
Enzyme17ß-HSD1 catalyzes reduction of estrone to estradiol. Its overexpression in estrogen responsive tissues is related to the development of breast cancer and endometriosis. We have discovered that simple coumarines prepared by Suzuki-Miyaura cross coupling reaction significantly inhibit 17ß-HSD1 in an recombinant enzyme assay with high selectivity over 17ß-HSD2. The best inhibitors in series were 7-phenyl-3-acetyl coumarin derivatives with the most potent compound having IC50 value of 268 nM and good selectivity over 17ß-HSD2 receptors.
COBISS.SI-ID: 27732441
DC-SIGN antagonists (inhibitors) are potential antiviral and antibacterial agents. To evaluate their biological effect, new robust, precise, and fast assay is needed. We have invented the assay that measures inhibition of human dendritic cell adhesion on mannan-coated microtiter plates. The assay is robust, accurate and reproducible. The format of the assay makes it suitable for screening of a large number of compounds, determination of inhibitory constants (IC50) and fast discovery of new DC-SIGN antagonists.
COBISS.SI-ID: 2834545
We demonstrate the correlation of toxic effect of Thiopurine therapy with polymorphisms in genes coding for TPMT, MTHFR and TYMS. The study demonstrates the need for developing pharmacogenomic strategies of metabolic networks, instead of pharmacogenetic approaches addressing the issue of correlation of polymorphisms in a single gene with a observed complex effect of a given medicine.
COBISS.SI-ID: 2739825
We have discovered novel benzylidenerhodanine and benzylidene-thiazolidine-2,4-dione multitarget inhibitors of bacterial Mur ligases and identified their inhibitory action on intracellular steps of peptidoglycan biisynthesis by means of enzyme kinetics and NMR interaction studies.
COBISS.SI-ID: 2743921