| Abstract |
The theme comprises a synthesis of analogues of natural compounds, e.g. nucleosides (but not essentially), bearing a triazine, thiazole or thiadiazole heterocycle (free or condensed with another heterocycle). Under certain circumstances, these pharmacophores can inhibit methyltrasferases (DNA-, histone-MT) through their specific interaction with the cysteine –SH group at the enzyme active site and thus reactivate gene expression (e.g. the genes silenced by aberrant methylation in tumor cells). The mentioned types of compounds also inhibit other enzymes with the cysteine thiol on an exposed place (e.g. cathepsin B), which extends their therapeutic potential. The target compounds will be tested for antitumor, antiviral and antibacterial activity, for their influence on the cell cycle and gene expression, and possibly, their mechanism of action could be further studied. Thus, it is probable that a structural activity study will comprise a part of the Ph. D. thesis. The conception of the project is flexible enough to pursue other attractive targets, if they emerge in the course of the work.
Moreover, polar structures with biological activity will be further transformed to appropriate prodrug forms to improve their bioavailability.
The focus of the work lies in organic synthesis especially in the chemistry of heterocyclic compounds, nucleosides and peptides, and in the basic knowledge of biochemistry with the accent to the potential activity of the designed compounds.
Our laboratory is very well and modern equipped, quite sufficiently for the synthetic work. All services for the structural analysis (NMR, MS, IR, elemental analysis etc.) are available at a high level.
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