Abstract：OBJECTIVE To design and synthesize a new kind of highly water-soluble platinum antitumor compounds, and then evaluate their cytotoxicity in order to confirm their antitumor efficacy. METHODS Diamide-diiodide platinum was firstly synthesized from potassium chloroplatinate, which was then reacted with Ag2SO4 to obtain intermediate Ⅰ. Using disodium 2-amino-alkyl malonate or N-substituted amino alkyl malonate as the intermediate Ⅱ, the two intermediates reacted at 1∶1 molar ratio to obtain the target compound Ⅲ in the presence of acid. RESULTS A new class of platinum compounds were synthesized, which had much better water solubility than that of the existing three-generation platinum compounds. Their antitumor efficacy was confirmed against a variety of tumor cell lines which was higher than that of carboplatin. Ⅲg was similar to cisplatin in antitumor efficacy on some tumor cell lines. Some target compounds were effective against cisplatin-resistant cell lines. CONCLUSION Currently in the clinical trial, the target compound Ⅲg is a new platinum-base antitumor candidate, which exhibits good water solubility and antitumor efficacy in vitro, and the LD50 based on mice shows its lower toxicity than that of cisplatin and carboplatin in vivo.
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