Synthesis and evaluation of platinum complexes with potential antitumor activity

Abstract A novel series of platinum (II) complexes was synthesized and the complexes were evaluated for their in vitro cytotoxicity against four human cancer cells lines. Five platinum complexes showed activity against at least one tumor cell line. Complexes 3 and 6 were promising, being active, at micromolar concentrations, against all the assayed tumor cell lines. Compound 3 was selected for further studies in mice with Ehrlich solid tumors and it was able to reduce the rate of tumor growth significantly during the first seven days. However, at the end of the experiments, there was no significant difference between the group of animals treated with 3 and the control group. The low solubility of the compound in the assay conditions can explain, at least in part, these results.

Clinical study of MRP and LRP mRNA expression in peple with human non-small cell lung cancer after cisplatin chemotherapy / 中国生化药物杂志

Objective To investigate the mRNA expression of the multidrug resistance associated protein and lung resistance protein in human non-small cell lung cancer tissues and their relationship with cis-platinum. Methods 13 samples were collected from patients with non small cell lung cancer before and after chemotherapy, the mRNA expression of MRP and LRP were detected using RT-PCR method, correlation between two genes were studied by Logistic regression analysis. Results Compared with before cisplatin chemotherapy, MRP and LRP expression of patients were increased after chemotherapy(P<0.05).Logistic regression analysis showed that there is no correlation between the two genes(r=0.036,P<0.05). Conclusion Cisplatin chemotherapy can increase the mRNA expression of MRP and LRP, and there is no correlation between the two genes.

Antitumor activity of five new platinum complexes having a glycolate leaving ligand

In an attempt to develop a new anticancer platinum complex with greater or equivalent antitumor activity but reduced side effects compared with cisplatin (CDDP), a series of new platinum complexes having a glycolate leaving ligand was synthesized. Among them, five complexes were selected for further development on the basis of adequate water solubility, low nephrotoxicity and high antitumor activity in a murine system. The chemosensitivity of these five complexes was examined in MTT assay against two human pulmonary adenocarcinoma cell lines, PC-9 and PC-14, and two human stomach adenocarcinoma cell lines, MKN-45 and KATO III. Their IC50 and relative antitumor activity (RAA) values were compared with those of CDDP and 254-S, a second-generation platinum complex with a glycolate leaving ligand under phase III clinical trial. The lowest mean IC50 value was observed in CDDP, followed by SKI 2034R and SKI 2033R. In this study, the antitumor activity was evaluated in terms of RAA values and SKI 2034R showed the highest RAA value. The order of RAA values was SKI 2034R > CDDP > SKI 2032R > SKI 2033R > SKI 2030R > SKI 2029R > 254-S. Based on the RAA order, we have recommended SKI 2034R as the most promising candidate for further development of a clinically useful platinum complex.