Evaluation of Pharmacological Activity of Heterobimetallic Coordination Compounds Containing N, N-Bis (2-hydroxyethyl)-Ethylenediamine on HT29, HeLa, C6 and Vero cells

The present study was conducted in order to investigate the pharmacological activities of three heterobimetallic coordination compounds: [Cd(N-bishydeten)2][Ni(CN)4] (C1), [Cu2(N-bishydeten)2Co(CN)6].3H2O (C2), and K[Cd(N-bishydeten)Co(CN)6].1.5H2O (C3) (N-bishydeten = N,N-bis(2-hydroxyethyl)-ethylenediamine). This paper describes the ability of complexes to inhibit cell growth, cell migration and human topoisomerase I and to interact with DNA/BSA; this paper also evaluates the potential mechanisms of action exhibited by these compounds via the use of TUNEL, IHC, DNA fragmentation and restriction endonuclease inhibitor activity techniques. Studies on HT29, HeLa, C6 and Vero cells revealed that each compound demonstrated significant antiproliferative activity in conjunction with regressed cell migration velocity and caused apoptotic changes in cell surface morphology such as cell rounding, membrane blebbing and blistering followed by DNA fragmentations. There is strong data to suggest that the mechanisms of action exhibited by these compounds are associated with their DNA/BSA binding features. The IC50 and binding constant range for the compounds are 20-180 µM and 1.2-3.2 x 104 M-1, respectively. Moreover, we observed that these compounds alter the P53-Bcl-2 ratio, indicating differentiation in cellular fate leading to cell death. Furthermore, they also inhibit the relaxation activity of human topoisomerase I which regulates the topological states of the DNA and inhibit KpnI or BamHI restriction endonucleases. Both effects of these compounds may be used in combination with adjuvant therapy for cancer. In conclusion, preliminary information demonstrates that these compounds have found to exhibit effective antiproliferative activity against cancer cell lines, indicating that they are a potent candidate for further pharmacological studies.