title: Design, synthesis and anticancer activity of diam(m)ine platinum(II) complexes bearing a small-molecular cell apoptosis inducer dichloroacetate.
abstract: Four new diam(m)ine platinum complexes containing the dichloroacetate moiety in 3-dichoroacetoxylcyclobutane-1,1-dicarboxylate as the leaving group were synthesized, characterized by elemental analysis as well as by ESI(+)-MS (electrospray ionization mass spectrometry in positive mode), FT-IR, (1)H- and (13)C-NMR, and evaluated for their in vitro anticancer activity against human lung cancer cell line (A549) and ovarian cancer cell lines (SK-OV-3, SK-OV-3/DDP). Diam(m)ines used in the present study belong to the carriers of six clinically approved platinum drugs. Among the complexes synthesized, complex 2, cis-[Pt(II)(1R,2R-diaminocyclohexane)·(3-dichoroacetoxylcyclobutane-1,1-dicarboxylate)] is the most promising in terms of water solubility and potential of being totally devoid of cross-drug resistance with cisplatin. Therefore, complex 2 was selected for the dichloroacetate release test. The test shows dichloroacetate can be efficiently released from complex 2 under physiological conditions via the hydrolysis of an ester bond bridging the dichloroacetate moiety and platinum pharmacophores together. Our study supports the further evaluation of this complex as a drug candidate.
authors.affiliation: State Key Laboratory for Platinum Group Metals, Kunming Institute of Precious Metals, 650106 Yunnan, PR China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Platinum Group Metals, Kunming Institute of Precious Metals, 650106 Yunnan, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, PR China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory for Platinum Group Metals, Kunming Institute of Precious Metals, 650106 Yunnan, PR China.
authors.forename: Shuqian
authors.initials: S
authors.lastname: Hou
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory for Platinum Group Metals, Kunming Institute of Precious Metals, 650106 Yunnan, PR China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, PR China. Electronic address: liguanglou1@126.com.
authors.forename: Liguang
authors.initials: L
authors.lastname: Lou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003999:Dichloroacetic Acid / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D003999:Dichloroacetic Acid
keywords: Anticancer activity; Dichloroacetate; Drug resistance; Platinum complexes