Picoplatin Derivatives for Anticancer Drug Development

Platinum-based complexes have been extensively investigated as chemotherapy drugs for multiple cancer types. Since the discovery of the first platinum drug cisplatin, another six platinum drugs have been approved for clinical use in USA and other countries. Cancer itself, however, is forever evolving, constantly producing cross resistance to the current medication. The chemotherapy drugs used in the past are soon becoming ineffective against tomorrow’s cancer. To discover new anticancer agents that can overcome the resistance and toxicity issues of the existing platinum drugs, a new family of platinum complexes are designed and synthesized based on Picoplatin, a platinum drug in clinical trials for solid tumors. More than 10 picoplatin derivatives with distinctive amine groups as non-leaving groups have been synthesized. All complexes were purified from either solvent washing, crystallization or chromatography. The platinum intermediates and final products were characterized using ESI-AccuTOF MS, HPLC, 1H NMR, 13C NMR, 195Pt NMR, and X-ray crystallography. Solubility of the platinum complexes in water and organic solvents was obtained using ICP-OES