From Sunscreen to Anticancer Agent: Ruthenium(II) Arene Avobenzone Complexes Display Potent Anticancer Activity

Pettinari, Riccardo; Marchetti, Fábio; Petrini, Agnese; Pettinari, Cláudio; Lupidi, Giulio; Smoleński, Piotr; Scopelliti, Rosario; Riedel, Tina; Dyson, Paul J.

doi:10.1021/acs.organomet.6b00694

Cited by 37 publications

(11 citation statements)

References 75 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upon addition of the complexes, the absorption peaks shifted toward longer wavelength and dramatically decreased at 218 nm. The decrease is due to the induced perturbation of the α-helix of BSA by the complexes . The red shift of the absorption spectra can be attributed to the effect of the polar solvent (water) .…”

Section: Resultssupporting

confidence: 81%

“…The decrease is due to the induced perturbation of the α-helix of BSA by the complexes. 47 The red shift of the absorption spectra can be attributed to the effect of the polar solvent (water). 48 With addition of metal complexes to BSA, there was no shift but a progressive decrease in the absorption peak of BSA at 278 nm was observed for complexes 1 and 3.…”

Section: ■ Results and Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Half-Sandwich Iridium and Ruthenium Complexes: Effective Tracking in Cells and Anticancer Studies

Guo

Tian

et al. 2018

Inorg. Chem.

View full text Add to dashboard Cite

Half-sandwich metal-based anticancer complexes suffer from uncertain targets and mechanisms of action. Herein we report the observation of the images of half-sandwich iridium and ruthenium complexes in cells detected by confocal microscopy. The confocal microscopy images showed that the cyclopentadienyl iridium complex 1 mainly accumulated in nuclei in A549 lung cancer cells, whereas the arene ruthenium complex 3 is located in mitochondria and lysosomes, mostly in mitochondria, although both complexes entered A549 cells mainly through energy-dependent active transport. The nuclear morphological changes caused by Ir complex 1 were also detected by confocal microscopy. Ir complex 1 is more potent than cisplatin toward A549 and HeLa cells. DNA binding studies involved interaction with the nucleobases 9-ethylguanine, 9-methyladenine, ctDNA, and plasmid DNA. The determination of bovine serum albumin binding was also performed. Hydrolysis, stability, nucleobase binding, and catalytic NAD + / NADH hydride transfer tests for complexes 1 and 3 were also carried out. Both complexes activated depolarization of mitochondrial membrane potential and intracellular ROS overproduction and induced cell apoptosis. Complex 3 arrested the cell cycle at the G 0 /G 1 phase by inactivation of CDK 4/cyclin D1. This work paves the way to track and monitor half-sandwich metal complexes in cells, shines a light on understanding their mechanism of action, and indicates their potential application as theranostic agents.

show abstract

Section: Resultssupporting

confidence: 81%

Section: ■ Results and Discussionmentioning

confidence: 94%

Half-Sandwich Iridium and Ruthenium Complexes: Effective Tracking in Cells and Anticancer Studies

Guo

Tian

et al. 2018

Inorg. Chem.

View full text Add to dashboard Cite

show abstract

“…Since the development of new metallodrugs for cancer treatment based on tertiary phosphines/aminophosphines [27,28,29,30,31,32] the interest for these types of ligands has reemerged. Both PTA and its derivatives have been applied in the synthesis of biologically active Pt(II/IV) [33,34,35,36,37], Au(I) [38,39,40], Ru(II) [41,42,43,44,45,46,47], Ag(I) [48,49,50,51] and Cu(I) [52,53,54,55] metal complexes. Indeed, phosphines can provide beneficial properties such as better stability in biological media (thus reducing undesired side reactions) and moldable affinity for polar and apolar environments in the cell (modifying the compounds transport across the membrane and their accumulation).…”

Section: Introductionmentioning

confidence: 99%

Pentafluorophenyl Platinum(II) Complexes of PTA and Its N-Allyl and N-Benzyl Derivatives: Synthesis, Characterization and Biological Activity

Sgarbossa

Śliwińska-Hill

ilva³

et al. 2019

Materials

View full text Add to dashboard Cite

From the well-known 1,3,5-triaza-phosphaadamantane (PTA, 1a), the novel N-allyl and N-benzyl tetrafuoroborate salts 1-allyl-1-azonia-3,5-diaza-7-phosphaadamantane (APTA(BF4), 1b) and 1-benzyl-1-azonia-3,5-diaza-7-phosphaadamantane (BzPTA(BF4), 1c) were obtained. These phosphines were then allowed to react with (Pt(μ-Cl)(C6F5)(tht))2 (tht = tetrahydrothiophene) affording the water soluble Pt(II) complexes trans-(PtCl(C6F5)(PTA)2) (2a) and its bis-cationic congeners trans-(PtCl(C6F5)(APTA)2)(BF4)2 (2b) and trans-(PtCl(C6F5)(BzPTA)2)(BF4)2 (2c). The compounds were fully characterized by multinuclear NMR, ESI-MS, elemental analysis and (for 2a) also by single crystal X-ray diffraction, which proved the trans configuration of the phosphine ligands. Furthermore, in order to evaluate the cytotoxic activities of all complexes the normal human dermal fibroblast (NHDF) cell culture were used. The antineoplastic activity of the investigated compounds was checked against the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa) and breast adenocarcinoma (MCF-7) cell cultures. Interactions between the complexes and human serum albumin (HSA) using fluorescence spectroscopy and circular dichroism spectroscopy (CD) were also investigated.

show abstract

“…However, NAMI-A failed in phase II tests, while KP1019 and its sodium salt KP1339 (sodium [trans-RuCl 4 (1H-indazole) 2 ]) are still under clinical trials. ,− Meanwhile, organometallic Ru(II) arene complexes such as [(C 6 H 5 Ph)-Ru(en)Cl][PF 6 ] (RM175, en = ethylenediamine) and [(p i PrC 6 H 4 Me)Ru(pta)Cl 2 ] (RAPTA-C, pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane) are also showing great therapeutic potential (Figure ). − In general, arene Ru(II) complexes present a “piano stool” geometry in which arene forms the seat and the other ligands resemble the legs. − The hydrophobic arene group can influence the cellular uptake and affect the kinetic reactivity of the ruthenium(II) complex, , while the rest coordination ligands may provide more opportunities to design anticancer agents with different modes of action. − …”

Section: Introductionmentioning

confidence: 99%

Anticancer Activity of Bifunctional Organometallic Ru(II) Arene Complexes Containing a 7-Hydroxycoumarin Group

et al. 2018

View full text Add to dashboard Cite

Three organometallic Ru(arene) compounds bearing 7-hydroxycoumarin have been designed and synthesized. Resulting Ru(II) complexes 2–4 showed potent cytotoxicity against the tested cancer cell lines, much higher than either the ligand L1 or unfunctionalized complex 1 alone. Further study indicated complexes 2–4 can activate the expression of Bax, induce cytochrome c release from the mitochondria, and finally activate caspase-3, hinting that these compounds probably induce cell apoptosis by mitochondrial pathway. Additional molecular docking study showed that complexes 2–4 have the potential to bind with the MEK1, and Western blot analysis confirmed that the Ru(II) complexes can prevent the phosphorylation of MEK1 and ERK1 in HCT116 cells, which helps us to further understand the anticancer mechanisms of the newly synthesized complexes. Overall, our research suggested that the ruthenium-coumarin complexes could induce cell apoptosis via inhibition of the mitochondrial and ERK signal pathways.

show abstract

From Sunscreen to Anticancer Agent: Ruthenium(II) Arene Avobenzone Complexes Display Potent Anticancer Activity

Cited by 37 publications

References 75 publications

Half-Sandwich Iridium and Ruthenium Complexes: Effective Tracking in Cells and Anticancer Studies

Half-Sandwich Iridium and Ruthenium Complexes: Effective Tracking in Cells and Anticancer Studies

Pentafluorophenyl Platinum(II) Complexes of PTA and Its N-Allyl and N-Benzyl Derivatives: Synthesis, Characterization and Biological Activity

Anticancer Activity of Bifunctional Organometallic Ru(II) Arene Complexes Containing a 7-Hydroxycoumarin Group

Contact Info

Product

Resources

About