(Carboxydiamine)Pt(II) complexes of a combretastatin A-4 analogous chalcone: the influence of the diamine ligand on DNA binding and anticancer effects

Published: MEDCHEMCOMM 2, 493-499 Authors: Zoldakova, M., Biersack, B., Kostrhunova, H., Ahmad, A., Padhye, S., Sarkar, FH., Schobert, R., Brabec, V. Year: 2011


The combretastatin A-4 analogue m-hydroxychalcone 2 was esterified with a (1-carboxyethane-2,3-diamine)dichloridoplatinum(II) fragment to give complex 6 which was more active against various cancer cell lines (IC(50) < 1 mu M) than its analogue 3 bearing a 6-aminomethylnicotinate ligand. Complex 6 bound to the same sites of DNA as cisplatin but caused a larger DNA unwinding angle and ten times more interstrand cross-links. Also, DNA lesions due to binding of 6 were only half as efficiently repaired as cisplatin-DNA adducts. Complex 6 also showed a much lower affinity to the platinum detoxifier glutathione.