general data

Project summary:

WE PROPOSE A COMPLEX INTER-/TRANS-DISCIPLINARY FUNDAMENTAL RESEARCH PROGRAM IN THE FIELD OF BIOMEDICAL APPLICATIONS OF METALLOCOMPLEXES. THE WIDE INTERNATIONAL INTEREST ON THIS TOPIC, AS WELL AS THE PERSPECTIVE OF OBTAINING NEW FUNDAMENTAL KNOWLEDGE AND THE POTENTIAL APPLICATIONS THEREOF, JUSTIFY SUCH A PROGRAM IN ROMANIA. THE PROJECT INVOLVES SPECIALISTS FROM DIVERSE FIELDS: CHEMISTRY, BIOCHEMISTRY, BIOLOGY, MEDICAL DOCTORS SPECIALIZED IN CLINICAL LABORATORY, MEDICAL ONCOLOGY, CHEMOTHERAPY, RADIOTHERAPY, SURGERY, ANATOMO-PATHOLOGY, PHARMACOLOGY, CELL BIOLOGY AND MATERIALS SCIENCE. INORGANIC AND ORGANOMETALLIC COMPOUNDS OF TRANSITION METALS AND OF MAIN GROUP ELEMENTS (E.G., GA) WITH HETEROCYCLIC LIGANDS CONTAINING ONE OR MORE SULFUR AND/OR NITROGEN ATOMS, CHIRAL AS WELL AS ACHIRAL (PHENOTHIAZINES, PYRIDINES, DIAZINES, TRIAZINES, TETRAZOLES), DIAZENIUM-DIOLATES, CALIXARENES, CALIXPYRROLES, DITHIOCARBAMATES, AND HETEROPOLYTOPIC LIGANDS (P/N, P/S, AS/N, AS/S), INCLUDING POTENTIAL NITRIC OXIDE GENERATORS, WILL BE SYNTHESIZED, CHARACTERIZED AND TESTED. IN ORDER TO FACILITATE TARGETED DELIVERY AND GRADUAL RELEASE OF THE ACTIVE COMPONENTS (HENCE, CONTROLLED CONCENTRATIONS THEREOF), COMPOUNDS/LIGANDS WILL BE ATTACHED TO PEPTIDIC MOIETIES OR OTHER BIOCOMPATIBLE MATRICES. THE FINAL GOAL IS TO IDENTIFY COMPOUNDS WITH ANTI-MITOTIC AND ANTI-PROLIFERATIVE EFFECT, WITH APPLICATIONS IN DEVELOPING NEW CHEMOTHERAPEUTICAL DRUGS AND RADIOSENSITIZING MATERIALS FOR USE IN CANCER THERAPY, AS WELL AS THE ELUCIDATION OF BIOCHEMICAL, IMMUNOLOGICAL, MOLECULAR, RADIOBIOLOGICAL, AND OXIDATIVE STRESS-RELATED ASPECTS OF THE INTERACTION OF METALS WITH LIVING CELLS. THIS WILL ENTAIL A SYSTEMATIC STUDY OF THE MOLECULAR-LEVEL INTERACTION BETWEEN METALLOPROTEINS (E.G., CYTOCHROME C, RELEVANT TO APOPTOSIS) AND THE NEWLY-SYNTHESIZED COMPOUNDS, AS WELL AS OF THE DEGREE TO WHICH THE LATTER MODULATE THE LEVELS OF STRESS AGENTS (E.G., NO, SUPEROXIDE) AND/OR AFFECT KEY STEPS IN APOPTOSIS OR CANCER.