Journal of Biological Inorganic Chemistry p. 1263 - 1275 (2015)
Update date:2022-08-28
Topics:
Qiu, Ling
Lv, Gaochao
Cao, Yang
Chen, Liping
Yang, Hui
Luo, Shineng
Zou, Meifen
Lin, Jianguo
Four novel platinum complexes, [Pt(en)]2ZL (1), [Pt(en)]2IPrBP (2), [Pt(en)]2MIBP (3) and [Pt(en)]2EIBP (4) [en = ethylenediamine; ZL = 1-hydroxy-3-(1H-imidazol-1-yl)ethane-1,1-diylbisphosphonic acid, commonly known as zoledronic acid; IPrBP = 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diylbisphosphonic acid; MIBP = 1-hydroxy-2-(2-methyl-1H-imidazol-1-yl)ethane-1,1-diylbisphosphonic acid; EIBP = 1-hydroxy-2-(2-ethyl-1H-imidazol-1-yl)ethane-1,1-diylbisphosphonic acid], were prepared and evaluated against five human cancer cell lines, including U2OS, A549, HCT116, MDA-MB-231 and HepG2. While exhibiting lower efficacy on the inhibition of cancer cell lines than cisplatin (CDDP), four complexes showed higher cytotoxicity than the corresponding ligands and relatively stronger cytotoxic effect on the hepatoma cell lines HepG2, and the complex 1 showed higher cytotoxicity than others on the whole. These complexes have better selectivity than the corresponding ligands in inhibiting hepatocarcinoma cells rather than normal liver cells, and the selective inhibitory effect of the complex 1 at the high concentration (100 μM) is better than that at the low concentration. Morphology studies exhibited typical characteristics of cell apoptosis and the cell cycle distribution analysis indicated that the complexes can inhibit cancer cells by inducing the cell cycle arrest at the G2/M phase, exhibiting a similar mechanism of action to CDDP. The binding interaction of complex with DNA has been explored by circular dichroism (CD) and UV-Vis absorption spectra, demonstrating these new complexes have moderate binding affinity for DNA. Graphical Abstract: Four platinum complexes based on imidazolyl-containing bisphosphonates with effective antitumor activity and low hepatotoxicity were designed and evaluated.[Figure not available: see fulltext.]
View MoreBeijing Apis Biotechnology Co., Ltd.
Contact:86-010-67856775-8551
Address:NO.4PUHUANGYU ROAD,FENTAI DISTRICT, BEIJING, CHINA
KA-SHING Business Trade Macau Co., Ltd.
Contact:00853-28430045
Address:23rd Floor, Block 3 La Cite, Areia Preta, Macao
Shouguang Haogang Chemical Co., Ltd.
Contact:86-0536-5672678
Address:Bohai Chemical Industrial Park,
LinHai Cina Chemical Co., LTD.
Contact:0576-85580989
Address:Pharma-chem zone,Duqiao,Linhai,Zhejiang,China
Contact:+44 7958 511245
Address:PO Box 469, Manchester, UK
Doi:10.1055/s-2004-822348
(2004)Doi:10.1021/acs.orglett.1c01109
(2021)Doi:10.1007/s10562-012-0931-0
(2013)Doi:10.1039/c9gc03449h
(2020)Doi:10.1080/00397910500521837
(2006)Doi:10.1039/c2dt32463f
(2013)