Department of Molecular Design and Biochemical Pharmacology

Research activity

The research activity of the Department of Molecular Design and Biochemical Pharmacology includes the following topics: 1) Synthesis, screening and mode of action of analogs of precursors of pyrimidine and purine nucleotides, analogs of protein and non-protein amino acids, modified neuroactive peptides; 2) Investigation on natural and synthetic inhibitors of UDP-glucuronosyltransferases (UGTs); 3) Synthesis and mechanism of action of new platinum complexes; 4) Molecular mechanism of action and appoptogenic effect of compounds with antitumor activity; 5) Antitumor effect and biochemical mechanisms of action of HSP90 molecular chaperon inhibitors; 6) Microbial diversity and activity in polluted environments. The research groups, engaged in these studies, are in close collaboration with each other.


The development of conformationally restricted unnatural amino acids and dipeptidemimetics is of major interest for the preparation of novel molecular architectures. We were interested in the design, synthesis and study of novel unnatural amino acids with more positively charges and bulky side chain groups than those of lysine, leucine and arginine. The unusual amino acids, which were synthesized by either solution or solid phase, were controled for enantiometric purity by HPLC, capillary electrophoresis (CE) and capillary electrochromatography (CEC).

UGTs catalyse the glucuronidation reaction, a major detoxification pathway in all vertebrates. We found that some widely used pesticides, as well as toxic compounds present in the human diet or used as drugs, significantly inhibit UGTs in vitro. Development of selective UGT inhibitors greatly enables the study of various UGTs and their function in vivo. We have synthesized and tested a series of 5’-O-amino and oligopeptide derivatives of uridine. The serine derivative proved to be a potent inhibitor of rat liver UGT and acted as a transition-state analog of the conjugation reaction.

Cis-diamminedichloroplatinum(II) (Cisplatin, DDP) is a widely used antitumor agent. The development of acquired resistance to DDP and the severe toxicity of these drug encouraged the search for new active platinum compounds exhibiting low toxicity. For the synthesis of new complexes, different types of nitrogen donor ligands, like cycloalkanecarboxylic acid hydrazides, 3-aminocycloalkanespiro-5-hydantoins as well as different benzoic acid hydrazides have been used.

The study of the molecular mechanisms of apoptosis in tumor cells upon treatment with clinically used, as well as with newly synthesized by us agents with antutumor activity, demonstrated a correlation between the ability of to induce apoptosis in vitro and their antitumor effect in vivo. In this connection, we intend to test the hypothesis that clinically important combined treatment of tumors with different agents induces synergistic activation of apoptotic mechanisms in cancer cells.

The inhibitors of HSP90 molecular chaperones emerged in recent years as a novel, unique class of antitumor agents with a specific profile and great potential. Because of the chemoprotective activity of several oncogenic proteins that are HSP90 clients, the combination of HSP90 inhibitors with standard chemotherapeutic agents could dramatically increase the in vivo efficacy of the therapy. The mechanism of action of these combinations will be studied on tumors having different expression profiles of oncogenic proteins. This may be of crucial importance for the choice of treatment strategy, especially against tumors resistant towards other cytostatics.

The microbial diversity and activity in environments polluted with heavy metals, and radionuclides is of great interest. Modern methods of molecular microbiology were applied to analyze the bacterial diversity of a Pb-Zn smelter works in south Bulgaria and several uranium mining wasters in East Germany, and the USA. In progress is the study on the microbial diversity in Bulgarian uranium wastes and oil contaminated sites. Many indigenous bacteria possessing Cu-, Cd-, Mn-, Pb-, Zn- and herbicides-tolerance were isolated. Such natiral isolates as Bacillus subtilis RG5 and Pseudomonas rhodesiae R5 are capable for biotransformation of Pb and phenol derivatives. They could be prospective for using in the bioremediation projects of industrially polluted environments.

International collaborations: University of Halle, Germany; University of Greifswald, Germany; Forschungszentrum Rossendorf, Germany; University of Graz, Austria; Czech Academy of Sciences; German Wool Institute, Technische Hochschule, Aachen, Germany.