P1-0208 — Annual report 2009
1.
Discovery of new inhibitors of the bacterial peptidoglycan biosynthesis enzymes MurD and MurF by structure-based virtual screening

Ligases MurC, MurD, MurE and MurF successively adding L-Ala, D-Glu, meso-A2pm or L-Lys, and D-Ala-D-Ala to the nucleotide precursor UDP-MurNAc are promising targets for antibacterial drug discovery. We have used the docking programme eHiTS for the virtual screening of 1,90 compounds from the NCI “Diversity Set” on MurD and MurF. The 50 top-scoring compounds for each enzyme were selected for biochemical evaluation. Virtual screening and subsequent in-vitro evaluation of the best ranked compounds provided 4 novel MurD inhibitors (best IC50 = 10 µM) and one novel MurF inhibitor (IC50 = 63 µM).

COBISS.SI-ID: 2505585
2.
Electrically tunable liquid crystal optical microresonators

A fluorescent compound with favourable physical – chemical properties was synthesized as an important component of an optical microresonator

COBISS.SI-ID: 22940455
3.
Dual role of serine protease inhibitors in induction of apoptosis

We have studied molecular mechanisms of cell death induced by inhibitors of serine proteases prepared by the programme team. We have delineated the dual role of these enzymes in the regulation of cell death.

COBISS.SI-ID: 2446961
4.
Novel aspects of DC-SIGN mediated intracellular signalling

An article on DC-SIGN intracellular signalling offers new insights into unknown mechamism of lectin signalling pathways.

COBISS.SI-ID: 2770545
5.
Review paper published in journal with high Impact factor

Since introduction of glitazones and epalrestat into clinical use for treatment of diabetes, rhodanines have become an interesting class of heterocycles, used also in our group for the synthesis of Mur inhibitores. Modifications of rhodanines constantly results in compounds with a wide spectrum of pharmacol. activities. Due to possible derivatization of the rhodanine ring, rhodanine-based compounds will certainly remain a privileged scaffold in drug discovery. We have reviewed their biological activities, structure activity relationship and selectivity against different targets.

COBISS.SI-ID: 2548337