Study of the anticancer properties of methyl- and phenyl-substituted carbon- and silicon-bridged ansa-titanocene complexes

Mijatović, Sanja; Bulatović, Mirna; Mojić, Marija; Stošić‐Grujičić, Stanislava; Miljković, Djordje; Maksimović‐Ivanić, Danijela; Gómez‐Ruiz, Santiago; Pinkas, Jiřı́; Horáček, Michal; Kaluđerović, Goran N.

doi:10.1016/j.jorganchem.2013.07.059

Cited by 9 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this respect, titanocene dichlorides bearing cyclopentadienyl rings substituted by alkyl and alkenyl, − methoxyalkyl, substituted aryl, silyl, and carboxylic acid esters were prepared and evaluated. Similarly, the effect of the bridge between cyclopentadienyl rings on the biological performance of ansa -titanocene dichlorides was recently elucidated. ,,, The Baird − and McGowan groups − have synthesized a family of water-soluble titanocene dichlorides bearing ionic alkyl and arylammonium substituents. These ionic complexes showed a remarkable cytotoxic activity against human ovarian cancer cell lines A2780, which was retained even against the cisplatin-resistant cell line A2780cis.…”

Section: Introductionmentioning

confidence: 99%

Titanocene Dihalides and Ferrocenes Bearing a Pendant α-d-Xylofuranos-5-yl or α-d-Ribofuranos-5-yl Moiety. Synthesis, Characterization, and Cytotoxic Activity

et al. 2014

Self Cite

View full text Add to dashboard Cite

Titanocene dichlorides of general formula [(η5-C5H5)(η5-C5H4R)TiCl2] (where R = 5-deoxy-1,2-di-O-isopropylidene-3-O-benzyl-α-d-xylofuranos-5-yl (Xylf) (8a); R = 5-deoxy-1,2-di-O-isopropylidene-3-O-benzyl-α-d-ribofuranos-5-yl (Ribf) (8b)) and [(η5-C5H4R)2TiCl2] (R = Xylf (9a); R = Ribf (9b)) were prepared by reaction of the corresponding lithium cyclopentadienides 7a,b with an equimolar amount of [(η5-C5H5)TiCl3] or a 0.5 mol amount of [TiCl4(THF)2]. Titanocene difluorides of the general formula [(η5-C5H4R1)(η5-C5H4R2)TiF2] (R1 = H and R2 = Ribf (10); R1 = R2 = Xylf (11a); R1 = R2 = Ribf (11b)) were obtained by fluorination of the corresponding titanocene dichlorides 8b and 9 with the fluorinating agent {2-(CH2NMe2)C6H4-κC,N}(n-Bu)2SnF in high yields. Alternatively, complexes 11 were prepared in a straightforward way by direct reaction of [TiF4(THF)2] with 2 equiv of the corresponding lithium cyclopentadienide 7a,b. Ferrocene complexes [(η5-C5H4R)2Fe] (R = Xylf (12a); R = Ribf (12b)) were synthesized by metathesis of 2 equiv of lithium cyclopentadienide 7a,b and 1 equiv of anhydrous FeCl2. Deprotection of the benzyl group in ferrocenes 12 proceeded cleanly by a catalytic hydrogenation on Pd/C and afforded the ferrocene diols [(η5-C5H4R)2Fe] (R = 5-deoxy-1,2-di-O-isopropylidene-α-d-xylofuranos-5-yl (Xylf-OH) (14a); R = 5-deoxy-1,2-di-O-isopropylidene-α-d-ribofuranos-5-yl (Ribf-OH) (14b)). A scaled up benzyl deprotection with Et3SiH as a hydrogen source led to the replacement of only one benzyl group, which gave the ferrocene alcohol [(η5-C5H4R1)(η5-C5H4R2)Fe] (R1 = Xylf and R2 = Xylf-OH (13)). The prepared complexes were characterized by elemental analysis, melting point determination, NMR, IR, and ESI-MS, and the molecular structure of 9b was determined by X-ray diffraction analysis. The cytotoxic activity of complexes 8–14 against A2780 and A2780cis cancer cells was evaluated by MTT tests. Titanocene difluorides 10 and 11 and ferrocene diol 14a showed cytotoxicity against A2780 cells in the medium to low micromolar range, while the most active species, 11b, displayed about 40% higher cytotoxicity against A2780cis in comparison to a cisplatin standard.

show abstract

Section: Introductionmentioning

confidence: 99%

Titanocene Dihalides and Ferrocenes Bearing a Pendant α-d-Xylofuranos-5-yl or α-d-Ribofuranos-5-yl Moiety. Synthesis, Characterization, and Cytotoxic Activity

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Dysfunction of mitochondrial membrane is one of the hallmarks of triggered intrinsic apoptotic pathway, starting as hyperpolarization and finalizing as a loss of membrane potential. Previously, some of us found that a class of ansa -titanocene complexes was able to provoke hyperpolarization prior the total mitochondrial collapse [ 24 ]. In the present study, staining of cells with propidium iodide permitted to disclose cells with abnormal shape, compressed volume of nuclei, and condensed chromatin, which is typical of apoptotic cells [ 25 ], besides cells with giant nuclei, indicating that 2b and 2d possess the ability to induce senescence ( Figure 4 E,F).…”

Section: Resultsmentioning

confidence: 99%

A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η5-C5Me4R} Complexes with Variable R Groups

Palo

Drača

Murrali

et al. 2021

IJMS

View full text Add to dashboard Cite

Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*) have been intensively investigated as anticancer drug candidates and hold much promise in this setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the antiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η5-C5Me4R)Cl(μ-Cl)]2 (R = Me, 1a; R = H, 1b; R = Pr, 1c; R = 4-C6H4F, 1d; R = 4-C6H4OH, 1e), their 2-phenylpyridyl mononuclear derivatives [Ir(η5-C5Me4R)(kN,kCPhPy)Cl] (2a–d), and the dimethylsulfoxide complex [Ir{η5-C5Me4(4-C6H4OH)}Cl2(κS-Me2S=O)] (3) were synthesized, structurally characterized, and assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5). Complexes 2b (R = H) and 2d (4-C6H4F) emerged as the most active ones and were selected for further investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumoricidal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species.

show abstract

“…All conditions are similar to those reported for other titanocene derivatives with cytotoxicity. 45,53,54…”

Section: Cell Lines and Cytotoxicity Assaysmentioning

confidence: 99%

Conjugates of titanocene with non-steroidal anti-inflammatory drugs: synthesis, unusual NMR characteristics, stability and cytotoxicity

Guk,

Gibadullina,

Moiseeva

et al. 2024

New J. Chem.

View full text Add to dashboard Cite

show abstract

Study of the anticancer properties of methyl- and phenyl-substituted carbon- and silicon-bridged ansa-titanocene complexes

Cited by 9 publications

References 35 publications

Titanocene Dihalides and Ferrocenes Bearing a Pendant α-d-Xylofuranos-5-yl or α-d-Ribofuranos-5-yl Moiety. Synthesis, Characterization, and Cytotoxic Activity

Titanocene Dihalides and Ferrocenes Bearing a Pendant α-d-Xylofuranos-5-yl or α-d-Ribofuranos-5-yl Moiety. Synthesis, Characterization, and Cytotoxic Activity

A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η5-C5Me4R} Complexes with Variable R Groups

Conjugates of titanocene with non-steroidal anti-inflammatory drugs: synthesis, unusual NMR characteristics, stability and cytotoxicity

Contact Info

Product

Resources

About