Catalpol, a DNA Polymerase Inhibitor from Buddleja cordobensis Hieron

PUNGITORE CR; JURI AYUB M; BORKOWSKI E; CIUFFO G; TONN CE

Mendoza, Argentina

Congreso; XX REUNIÓN ANUAL SOCIEDAD DE BIOLOGÍA DE CUYO; 2002

SOCIEDAD DE BIOLOGÍA DE CUYO

Both DNA polymerases and topoisomerases have been identified as a target for anticancer drug development. The iridoid glucoside. Catalpol was isolated from the shrub Buddleja cordobensis and the structure was elucidated using 1D and 2D NMR techniques. Catalpol was screened in order to detect potential taq DNA polymerase inhibitory activity handling polymerase chain reaction (PCR). This molecule showed a strong inhibition against taq DNA polymerase with IC50: 42mM. Chemical derivates such as peracetylcatalpol; 3,4-dihydrocatalpol; 10,6´-O-di-terbutyldifenylsilylcatalpol; 10,6´-O-di-oleylcatalpol, and 4´,6´-Oisopropylidenecatalpol were prepared in an attempt to modificate estereoelectronic factors. Structure-activity relationships will be discussed from Molecular Mechanic (MMFF), conformational analysis, and semi-empirical calculations (HOMO, LUMO and MEP) carried out with Spartan Pro software.