Topoisomerase I inhibition and antiproliferative activity of maslinic acid analogs

CARLOS R. PUNGITORE; LETICIA G. LEÓN; JOSÉ M. PADRÓN; CELINA GARCÍA; VÍCTOR S. MARTÍN; GLADYS M. CIUFFO; CARLOS E. TONN

Instituto Universitario de Bio-Orgánica “Antonio González” (IUBO), ULL, TENERIFE. España

Congreso; 3rdMeeting of Young Cancer Investigators of the Canaries (3rd YCIC); 2006

Instituto Canario de Investigaciones del Cáncer

DNA polymerases and DNA topoisomerases are essential for genome integrity and correct transmission of genetic information in all living organisms. DNA topoisomerases, that catalyse the interconversion of various topological states of DNA, were originally discovered as enzymes that change the super helical structure of closed circular DNA. Based on their functional mechanisms, DNA topoisomerases have been classified into two types. Type I DNA topoisomerases break and rejoin only one of the two strands during catalysis, while type II DNA topoisomerases break and rejoin both strands for each DNA strand-passing reaction. Herein, we report on the ability of maslinic acid and its diacetyl derivate to inhibit topo I. Additionally, the in vitro antiproliferative activity of said compounds was evaluated by measuring the growth inhibition of against the panel of human solid tumour cell lines A2780 (ovarian cancer), SW1573 (non-small cell lung cancer, NSCLC), WiDr (colon cancer), T-47D (breast cancer) and HBL-100 (breast cancer). These results suggest that maslinic acid and its diacetate behave as DNA topoisomerase I inhibitors and growth inhibitors against human cancer cell lines. This kind of compound could be a tool, not only to investigate DNA topoisomerases I activities but also, the computer-simulated drug design based on the chemical structure of these agents might be useful in the development of new anticancer agents.