title: Dialkyl bisphosphonate platinum(II) complex as a potential drug for metastatic bone tumor.
abstract: Bisphosphonates have high affinity for hydroxyapatite (HA), which is abundantly present in bone. Also, platinum complexes are known that have a wide spectrum of antitumor activities. The conjugate of bisphosphonate and a platinum complex might have HA affinity and antitumor activity, and become a drug for metastatic bone tumor. In this study, the authors synthesized platinum complexes that had dialkyl bisphosphonic acid as a ligand, and evaluated the possibility of the synthesized complexes as a drug for metastatic bone tumor. The synthesized dialkyl bisphosphonate platinum(II) complex was characterized, and its stability in an aqueous solution was also confirmed. The synthesized platinum complex showed higher HA affinity than other platinum complexes such as cisplatin and carboplatin in an experiment of adsorption to HA. In vitro, the platinum complex showed tumor growth inhibitory effect stronger than or equal to cisplatin, which is the most commonly used antitumor agent. Moreover, the platinum complex showed a bone absorption inhibitory effect on the osteoclast. These results suggest potential of dialkyl bisphosphonate platinum(II) complexes as a drug for metastatic bone tumor.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3–1–1 Maidashi, Higashi-ku, Fukuoka, Japan. nakatake.h@tmrc.co.jp
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nakatake
authors.forename: Hisao
authors.initials: H
authors.lastname: Ekimoto
authors.forename: Mariko
authors.initials: M
authors.lastname: Aso
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogawa
authors.forename: Asami
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suemune
mesh_terms: D000327:Adsorption; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016190:Carboplatin / Q000737:chemistry; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry; D056831:Coordination Complexes / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D004164:Diphosphonates / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D006801:Humans; D009362:Neoplasm Metastasis; D010010:Osteoclasts / Q000187:drug effects; D010984:Platinum / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004164:Diphosphonates; D010984:Platinum; D017886:Durapatite; D016190:Carboplatin; D002945:Cisplatin