酰胺官能化二茂钛的合成、结构与生物活性：改善其细胞毒性特性
Synthesis, Structure and Biological Activity of Amide-Functionalized Titanocenyls: Improving their Cytotoxic Properties.
作者信息
Gao Li Ming, Matta Jaime, Rheingold Arnold L, Meléndez Enrique
机构信息
Department of Chemistry, University of Puerto Rico, Mayagüez, PR 00681.
出版信息
J Organomet Chem. 2009 Dec 15;694(26):4134-4139. doi: 10.1016/j.jorganchem.2009.09.016.
Abstract
Nine amide-functionalized titanocenyls have been synthesized and characterized by spectroscopic and analytical methods and the solid state structure of Cp(CpCO-NH-C(6)H(4)-OCF(3))TiCl(2) was determined by single crystal X-ray diffraction. X-ray analysis of Cp(CpCO-NH-C(6)H(4)-OCF(3))TiCl(2) showed that titanium is in a pseudo tetrahedral geometry and contains a Ti-O(amide) coordination. In principle, Ti-O coordination should provide more hydrolytic stability to the corresponding titanocenyls than titanocene dichloride. The cytotoxic activities of these amide-functionalized titanocenyls on HT-29 colon cancer cell line were determined by MTT assay to elucidate structure-activity relationship. All complexes were more cytotoxic than titanocene dichloride and there is no correlation between the para substituents on the phenyl ring and their cytotoxicities.
摘要
已合成了九种酰胺官能化二茂钛，并通过光谱和分析方法对其进行了表征，且通过单晶X射线衍射确定了Cp(CpCO-NH-C(6)H(4)-OCF(3))TiCl(2)的固态结构。对Cp(CpCO-NH-C(6)H(4)-OCF(3))TiCl(2)的X射线分析表明，钛处于假四面体几何构型，且含有Ti-O(酰胺)配位。原则上，与二氯二茂钛相比，Ti-O配位应为相应的二茂钛基提供更高的水解稳定性。通过MTT法测定了这些酰胺官能化二茂钛对HT-29结肠癌细胞系的细胞毒性活性，以阐明构效关系。所有配合物的细胞毒性均比二氯二茂钛更强，且苯环上的对位取代基与其细胞毒性之间没有相关性。
相似文献
1
Synthesis, Structure and Biological Activity of Amide-Functionalized Titanocenyls: Improving their Cytotoxic Properties.
J Organomet Chem. 2009 Dec 15;694(26):4134-4139. doi: 10.1016/j.jorganchem.2009.09.016.
2
Cytotoxic properties of titanocenyl amides on breast cancer cell line mcf-7.
Met Based Drugs. 2010;2010:286298. doi: 10.1155/2010/286298. Epub 2010 May 4.
3
Structure-activity studies of Ti(IV) complexes: aqueous stability and cytotoxic properties in colon cancer HT-29 cells.
J Biol Inorg Chem. 2008 Jun;13(5):685-92. doi: 10.1007/s00775-008-0353-z. Epub 2008 Feb 21.
4
Synthesis, Ti(IV) intake by apotransferrin and cytotoxic properties of functionalized titanocene dichlorides.
J Biol Inorg Chem. 2007 Sep;12(7):959-67. doi: 10.1007/s00775-007-0268-0. Epub 2007 Jun 14.
5
Titanium(IV) complexes: cytotoxicity and cellular uptake of titanium(IV) complexes on caco-2 cell line.
Toxicol In Vitro. 2010 Feb;24(1):178-83. doi: 10.1016/j.tiv.2009.09.010. Epub 2009 Sep 20.
6
Study of the cytotoxicity and particle action in human cancer cells of titanocene-functionalized materials with potential application against tumors.
J Inorg Biochem. 2012 Jan;106(1):100-10. doi: 10.1016/j.jinorgbio.2011.09.033. Epub 2011 Oct 5.
7
Synthesis and cytotoxicity studies of steroid-functionalized titanocenes as potential anticancer drugs: sex steroids as potential vectors for titanocenes.
J Biol Inorg Chem. 2010 Aug;15(6):851-9. doi: 10.1007/s00775-010-0649-7. Epub 2010 Mar 28.
8
Development of bimetallic titanocene-ruthenium-arene complexes as anticancer agents: relationships between structural and biological properties.
J Med Chem. 2010 Oct 14;53(19):6923-33. doi: 10.1021/jm1004804.
9
Titanocene-phosphine derivatives as precursors to cytotoxic heterometallic TiAu2 and TiM (M = Pd, Pt) compounds. Studies of their interactions with DNA.
Inorg Chem. 2011 Nov 7;50(21):11099-110. doi: 10.1021/ic201647h. Epub 2011 Sep 29.
10
Different ortho and para electronic effects on hydrolysis and cytotoxicity of diamino bis(phenolato) "salan" Ti(IV) complexes.
Inorg Chem. 2011 Feb 7;50(3):1030-8. doi: 10.1021/ic101693v. Epub 2011 Jan 7.
引用本文的文献
1
A Comprehensive Review on the Development of Titanium Complexes as Cytotoxic Agents.
Curr Top Med Chem. 2024;24(24):2117-2128. doi: 10.2174/0115680266317770240718080512.
2
Expanding the Therapeutic Potential of the Iron Chelator Deferasirox in the Development of Aqueous Stable Ti(IV) Anticancer Complexes.
Inorg Chem. 2017 Jul 17;56(14):7788-7802. doi: 10.1021/acs.inorgchem.7b00542. Epub 2017 Jun 23.
3
A ubiquitous metal, difficult to track: towards an understanding of the regulation of titanium(iv) in humans.
Metallomics. 2017 Apr 19;9(4):346-356. doi: 10.1039/c6mt00223d.
4
The addition of a pregnenolone pendant group enhances the anticancer properties of titanocene dichloride in a mcf-7 xenograft model.
Anticancer Res. 2014 Apr;34(4):1609-15.
5
On the discovery, biological effects, and use of Cisplatin and metallocenes in anticancer chemotherapy.
Bioinorg Chem Appl. 2012;2012:140284. doi: 10.1155/2012/140284. Epub 2012 Jul 12.
6
Host-Guest Interactions between Calixarenes and Cp(2)NbCl(2).
J Organomet Chem. 2011 Jul 1;696(13):2519-2527. doi: 10.1016/j.jorganchem.2011.03.021.
7
Cytotoxic activity of the titanium alkoxide (OPy)(2)Ti(4AP)(2) against cancer colony forming cells.
Invest New Drugs. 2012 Feb;30(1):114-20. doi: 10.1007/s10637-010-9530-3. Epub 2010 Sep 7.
8
Cytotoxic properties of titanocenyl amides on breast cancer cell line mcf-7.
Met Based Drugs. 2010;2010:286298. doi: 10.1155/2010/286298. Epub 2010 May 4.
9
Synthesis and cytotoxicity studies of steroid-functionalized titanocenes as potential anticancer drugs: sex steroids as potential vectors for titanocenes.
J Biol Inorg Chem. 2010 Aug;15(6):851-9. doi: 10.1007/s00775-010-0649-7. Epub 2010 Mar 28.
本文引用的文献
1
Pseudo-halide derivatives of titanocene: synthesis and cytotoxicity studies.
Metallomics. 2009 Nov;1(6):511-7. doi: 10.1039/b911753a. Epub 2009 Sep 2.
2
Carbonyl-substituted titanocenes: a novel class of cytostatic compounds with high antitumor and antileukemic activity.
Chemistry. 2008;14(14):4160-3. doi: 10.1002/chem.200800407.
3
Structure-activity studies of Ti(IV) complexes: aqueous stability and cytotoxic properties in colon cancer HT-29 cells.
J Biol Inorg Chem. 2008 Jun;13(5):685-92. doi: 10.1007/s00775-008-0353-z. Epub 2008 Feb 21.
4
Analyses of Titanocenes in the spheroid-based cellular angiogenesis assay.
Toxicol In Vitro. 2008 Mar;22(2):531-4. doi: 10.1016/j.tiv.2007.09.014. Epub 2007 Sep 29.
5
Synthesis, Ti(IV) intake by apotransferrin and cytotoxic properties of functionalized titanocene dichlorides.
J Biol Inorg Chem. 2007 Sep;12(7):959-67. doi: 10.1007/s00775-007-0268-0. Epub 2007 Jun 14.
6
Antiproliferative activity of Titanocene Y against tumor colony-forming units.
Anticancer Drugs. 2007 Mar;18(3):317-21. doi: 10.1097/CAD.0b013e3280115f86.
7
Novel titanocene anti-cancer drugs and their effect on apoptosis and the apoptotic pathway in prostate cancer cells.
Apoptosis. 2006 Jul;11(7):1205-14. doi: 10.1007/s10495-006-6796-1.
8
A modular and efficient synthesis of functional titanocenes.
J Am Chem Soc. 2005 Aug 24;127(33):11622-3. doi: 10.1021/ja054185r.
9
Water-soluble titanocene complexes with sulfur-containing amino acids: synthesis, spectroscopic, electrochemical and Ti(IV)-transferrin interaction studies.
J Biol Inorg Chem. 2005 Mar;10(2):94-104. doi: 10.1007/s00775-004-0614-4. Epub 2004 Dec 24.
10
Antitumor titanium compounds.
Mini Rev Med Chem. 2004 Jan;4(1):49-60. doi: 10.2174/1389557043487565.
Zotero 插件