Synthesis And In Vitro Cytotoxicity Of Novel Dichloroplatinum(Ⅱ) Complexes Of Podophyllotoxin

Cisplatin was approved as a first-line treatment for ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. VP-16was an important component in chemotherapy regimes for the treatment of non-small-cell lung carcinoma and small-cell lung carcinoma. In current clinical treatment, many anticancer drugs have to be combined to achieve the desired therapeutic effect that single drug fail to do this. Combination chemotherapy of cisplatln and VP-16is always applied for treatment of non-small-cell lung carcinoma, malignant lymphoma and other cancer. Three dichloroplatinum (Ⅱ) complexes of podophyllotoxin were synthesized and evaluated for cytotoxicity against six cell lines. Complex cis-[4a-O-(2",3"-diaminopropanoyl)-podophyllotoxin] dichloride platinum (Ⅱ)9a displayed more potent cytotoxicity against VP-16sensitive (A-549, HeLa, HCT-8, Hep-G2, K562) and VP-16resistant (ADM/K562) cell lines compared to9b and9c. Flow cytometric analysis exhibited that9a induced cell cycle arrest in the G2/M phase, and apoptosis accompanied mitotic catastrophe in HeLa cells. Furthermore,9a inhibited the formation of microtubulin in A-549cells and exhibit potent in vitro DNA cleavage capabilities. These results suggested that platinum (Ⅱ) complex of podophyllotoxin interact with DNA and futher induce cell apoptosis same as cisplatin, but they also have the same characteristics as podophyllotoxin.