Dialkyl Bisphosphonate Platinum(II) Complex as a Potential Drug for Metastatic Bone Tumor
Dialkyl Bisphosphonate Platinum(II) Complex as a Potential Drug for Metastatic Bone Tumor
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DOI：
10.1248/cpb.59.710
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发表时间：
2011-06-01
影响因子：
1.7
通讯作者：
Suemune, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakatake, Hidetoshi;Ekimoto, Hisao;Suemune, Hiroshi
双膦酸盐对羟基磷灰石（HA）具有高亲和力，羟基磷灰石大量存在于骨中。此外，已知铂络合物具有广谱抗肿瘤活性。双膦酸盐与铂配合物的偶联物可能具有HA亲和性和抗肿瘤活性，有望成为治疗骨转移瘤的药物。在这项研究中，作者合成了铂配合物，具有二烷基双膦酸作为配体，并评估合成的配合物作为转移性骨肿瘤的药物的可能性。合成的二烷基双膦酸盐铂（II）配合物的特征在于，其在水溶液中的稳定性也得到了证实。在吸附HA的实验中，合成的铂配合物显示出比其他铂配合物如顺铂和卡铂更高的HA亲和力。在体外，铂配合物显示出比顺铂更强或等同于顺铂的肿瘤生长抑制作用，顺铂是最常用的抗肿瘤剂。此外，铂络合物对破骨细胞显示出骨吸收抑制作用。这些结果表明二烷基二膦酸盐铂（II）配合物作为转移性骨肿瘤的药物的潜力。
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.