Cis-diamminedichloridoplatinum(II) (
cisplatin), which was first introduced as a clinical
anticancer agent in the 1970s, is still among the most-utilized agents in current
cancer chemotherapy. The discovery of
cisplatin antitumor activity has catalyzed
drug discovery research on antitumor
platinum coordination compounds with improved efficacy. Some of new compounds show fewer side effects or expanded clinical applications. Apart from some clinical inconveniences, such as side effects, the high therapeutic efficacy of
platinum-based agents implies that further modifications may lead to more effective anticancer
platinum drugs which are effective against
cancers that are typically resistant to
chemotherapy, such as
pancreatic cancer, and
platinum-refractory
cancer. Most of the
cisplatin analogs cause cross-resistance to
cisplatin, probably because of the similar
biological consequences. It is suggested that
platinum complexes which interact with
DNA; the most probable target molecule, through a mechanism different from that of
cisplatin can provide unique anticancer spectra required for next-generation anticancer drugs. Therefore, we synthesized a series of azolato-bridged dinuclear Pt(II) complexes with a general formula, [{cis-Pt(NH(3))(2)}(2)(µ-
OH)(µ-azolato)](2+), which can form 1,2-intrastrand crosslinks with a minimal
DNA distortion, whereas clinical
platinum-based drugs provide 1,2-intrastrand crosslink with severe
DNA distortion. Indeed, they exhibit much higher in vitro cytotoxicity than
cisplatin, and we have recently found one of the dinuclear Pt(II) complexes exhibits markedly high in vivo antitumor efficacy against
pancreatic cancer. Here, I update our
drug-discovery research on the series of azolato-bridged dinuclear Pt(II) complexes that may be more effective and safer than current anticancer chemotherapeutic agents.