Laboratory OF BIOLOGICAL ACTIVE COMPOUNDS
UniversityofSofia, Faculty of Chemistry, Department of Applied Organic Chemistry
Head of group: Assoc. Prof. Ognyan Petrov, PhD
The Group of Biological Active Compounds specializes in the field of organic synthesis including preparation, structural characterization and biological evaluation of novel compounds. The main activities are associated with the development of new synthetic methods, design and synthesis of new classes of heterocyclic derivatives, combining different pharmacophore fragments and investigation of their biological activity. The laboratory has established collaborations with various groups of Faculty of Pharmacy (MedicalUniversity,Sofia,Bulgaria),InstituteofMolecular Biology(BulgarianAcademyof Sciences) and University Paul Verlaine (Metz,France).
In the last 5 years, our efforts are focused to obtain stilbene and chalcone derivatives as potential anticancer agents. This is due to the fact that one of the most promising agents for cancer therapy is naturally-occurring combretastatin A-4 (CA-4). The CA-4 is a very attractive compound because of its simple structure and high cytotoxic activity against a variety of human cancer cell lines. The cis-stilbene CA-4 is a potent anticancer drug and represents a new class of therapeutic compounds known as vascular disrupting agents. At present, we synthesize a few series of new heterocycle analogues of CA-4 containing benzoxazolone or benzothiazolone moiety, which could adjoint important pharmacological properties. The results obtained from the conducted bioassay showed that these compounds exerted cytotoxic effects on various cancer cell lines in a concentration-dependent manner, causing 50% inhibition of the malignant cell proliferation at low micromolar concentrations. Several stilbene derivatives displayed potent cytotoxic activity against HepG2 cells with IC50 values in the nanomolar range. The ability of these heterocyclic stilbene, containing benzoxa(thia)zolone ring, to inhibit tubulin polymerization has been evaluated by fluorescent microscopy and flow-cytometry. The results showed that HepG2 were arrested at a pro-metaphase stage, with formation of condensed chromosomes and unnormal spindle formation. The arrest of cell cycle at G2/M phase also triggered the apoptotic cell death in HepG2 line. The heterocyclic analogues of CA-4 showed a potent anticancer activity and it is important because new anticancer therapeutics may emerge from these efforts.
- Petrov, O., Y. Ivanova, M. Gerova, SOCl2/EtOH: Catalytic system for synthesis of chalcones, Catalysis Communications, 9 (2008) 315–316
- Petrov, O, Y. Ivanova, G. Momekov, V. Kalcheva, New Synthetic Chalcones: Cytotoxic Mannich Bases of 6-(4-Chlorocinnamoyl)-2(3H)-benzoxazolone, Lett. Drug Design Discov. 5, 358-361 (2008)
- Petrov, O., M. Gerova, K. Petrova, Y. Ivanova, New Imidazole Derivatives of 2(3H)‑Benzazolones as Potential Antifungal Agents, J. Heterocycl. Chem., 46 (1), 44-48 (2009).
- Tzanova, Tz., M. Gerova, O. Petrov, M. Karaivanova, D. Bagrel, Synthesis and antioxidant potential of novel synthetic benzophenone analogues, Eur. J. Med. Chem., 44, 2724-2730 (2009)
- Ivanova, Y., G, Momekov, O. Petrov, Synthesis of Novel Substituted 1,3-diarylpropenone Derivatives and their In Vitro Cytotoxic Activity, Lett. Drug Design Discov. 6, 5 (2009)