| Title | Bifunctional bisphosphonate derivatives and platinum complexes with high affinity for bone hydroxyapatite. |
|---|---|
| Authors | Sun, Y.; Chen, L.; Wu, X.; Ding, Q. |
| Journal | Bioorg Med Chem Lett |
| DOI | 10.1016/j.bmcl.2016.12.050 |
| Abstract |
A series of ethylenediamine/1,3-propanediamine derivatives containing bifunctional bisphosphonate substituents and their corresponding dichloroplatinum(II) complexes have been synthesized and characterized by elemental analysis, (1)H NMR, (13)C NMR, (31)P NMR, and HRMS spectra. Based on WST-8 assay with CCK-8, in general, the newly synthesized dichloroplatinum complexes 1-6 showed higher in vitro antitumor activity than platinum-free compounds L1-L6 against three tumor cell lines (especially osteosarcoma MG-63). According to hydroxyapatite binding experiment, complexes 2, 3, and 6 showed much higher affinity (K'=3.7, 4.0, and 3.0, respectively) for bone hydroxyapatite than cisplatin (K'0.1), comparable to zoledronate (K'=2.8). It can be found that representative complex 2 with high cytotoxicity and in vitro antiproliferative activity against osteosarcoma cell line, as well as promising hydroxyapatite binding ability has been screened as a potential bone-targeting antitumor agent for subsequent in vivo study. In addition, flow cytometry experiment was applied to investigate the mode of action of representative complex 2. |
See more Platinum products. Platinum (atomic symbol: Pt, atomic number: 78) is a Block D, Group 10, Period 6 element with an atomic weight of 195.084. The number of electrons in each of platinum's shells is [2, 8, 18, 32, 17, 1] and its electron configuration is [Xe] 4f14 5d9 6s1. The platinum atom has a radius of 139 pm and a Van der Waals radius of 175 pm. 
Platinum was discovered and first isolated by Antonio de Ulloa in 1735. It is one of the rarest elements in the earth's crust, occurring at a concentration of only 0.005 ppm. Platinum is found uncombined as a free element and alloyed with iridium as platiniridium. In its elemental form, platinum has a grayish white appearance. It is highly resistant to corrosion: the metal does not oxidize in air at any temperature. It is generally non-reactive, even at high temperatures. The origin of the name "platinum" comes from the Spanish word platina, meaning silver.