Maikoo, Sanam, Xulu, Bheki, Mambanda, Allen +4 more · 2022 · ChemMedChem
Maikoo, Sanam, Xulu, Bheki, Mambanda, Allen, Mkhwanazi, Ntando, Davison, Candace, de la Mare, Jo‐Anne, Booysen, Irvin Noel Show less
Herein we illustrate the formation and characterization of new paramagnetic ruthenium compounds, trans-P-[RuCl(PPh3 )2 (pmt)]Cl (1) (Hpmt=1-((pyridin-2-yl)methylene)thiosemicarba Show more
Herein we illustrate the formation and characterization of new paramagnetic ruthenium compounds, trans-P-[RuCl(PPh3 )2 (pmt)]Cl (1) (Hpmt=1-((pyridin-2-yl)methylene)thiosemicarbazide), trans-P-[RuCl(PPh3 )2 (tmc)]Cl (2) (Htmc=1-((thiophen-2-yl)methylene)thiosemicarbazide) and a diamagnetic ruthenium complex, cis-Cl, trans-P-[RuCl2 (PPh3 )2 (btm)] (3) (btm=2-((5-hydroxypentylimino)methyl)benzothiazole). Agarose gel electrophoresis experiments of the metal compounds illustrated dose-dependent binding to gDNA by 1-3, while methylene blue competition assays suggested that 1 and 2 are also DNA intercalators. Assessment of the effects of the compounds on topoisomerase function indicated that 1-3 are capable of inhibiting topoisomerase I activity in terms of the ability to nick supercoiled plasmid DNA. The cytotoxic activities of the metal complexes were determined against a range of cancer cell lines versus a non-tumorigenic control cell line, and the complexes were, in general, more cytotoxic towards the cancer cells, displaying IC50 values in the low micromolar range. Time-dependent stability studies showed that in the presence of strong nucleophilic species (such as DMSO), the chloride co-ligands of 1-3 are rapidly substituted by the former as proven by the suppression of the substitution reactions in the presence of an excess amount of chloride ions. The metal complexes are significantly stable in both DCM and an aqueous phosphate buffer containing 2 % DMSO. Show less
Dömötör, Orsolya, Teixeira, Ricardo G., Spengler, Gabriella +7 more · 2023 · Journal of Inorganic Biochemistry
Dömötör, Orsolya, Teixeira, Ricardo G., Spengler, Gabriella, Avecilla, Fernando, Marques, Fernanda, Lenis-Rojas, Oscar A., Matos, Cristina P., de Almeida, Rodrigo F.M., Enyedy, Éva A., Tomaz, Ana Isabel Show less
With the aim to incorporate pharmacophore motifs into the Ru(II)-polypyridyl framework, compounds [Ru(II)(1,10-phenantroline)2(2-(2-pyridyl)benzo[b]thiophene)](CF3SO3) Show more
With the aim to incorporate pharmacophore motifs into the Ru(II)-polypyridyl framework, compounds [Ru(II)(1,10-phenantroline)2(2-(2-pyridyl)benzo[b]thiophene)](CF3SO3)2 (1) and [Ru(II)(1,10-phenantroline)2(2-(2-pyridyl)benzimidazole)](CF3SO3)2 (2) were prepared, characterized and tested for their antitumor potential. The solid-state structure of the compounds was confirmed by single-crystal X-ray diffraction analysis. The solution behavior of both complexes was investigated, namely their solubility, stability, and lipophilicity in physiological mimetic conditions, as well as an eventual uptake by passive diffusion. In vitro anticancer activity of the complexes on ovarian and different colon cancer cells and apoptosis induction by the complexes were studied. A slow transformation process was observed for complex 1 in aqueous solution when exposed to sunlight, while complex 2 undergoes deprotonation (pKa = 7.59). The lipophilicity of this latter complex depends strongly on the pH and ionic strength. In contrast, 1 is rather hydrophilic under various conditions. Complex 1 was highly cytotoxic on Colo-205 human colon (IC50 = 7.87 μM) and A2780 ovarian (IC50 = 2.2 μM) adenocarcinoma cell lines, while 2 displayed moderate anticancer activity (30.9 μM and 18.0 μM, respectively). The complexes induced late apoptosis and necrosis. Only a weak binding of the complexes to human serum albumin, the main transport protein in blood serum, was found. However, a more significant binding to calf thymus DNA was observed in UV-visible titrations and fluorometric dye displacement studies. Detailed analysis of fluorescence lifetime data collected for the latter systems reveals not only the partial intercalation of the complexes, but goes beyond the usual simplified interpretations. Show less
Brás, Ana Rita, Fernandes, Pedro, Moreira, Tiago +5 more · 2023 · Pharmaceutics
Brás, Ana Rita, Fernandes, Pedro, Moreira, Tiago, Morales-Sanfrutos, Julia, Sabidó, Eduard, Antunes, Alexandra M. M., Valente, Andreia, Preto, Ana Show less
Colorectal cancer (CRC) is among the most deadly cancers worldwide. Current therapeutic strategies have low success rates and several side effects. This relevant clinical problem requires the discover Show more
Colorectal cancer (CRC) is among the most deadly cancers worldwide. Current therapeutic strategies have low success rates and several side effects. This relevant clinical problem requires the discovery of new and more effective therapeutic alternatives. Ruthenium drugs have arisen as one of the most promising metallodrugs, due to their high selectivity to cancer cells. In this work we studied, for the first time, the anticancer properties and mechanisms of action of four lead Ru-cyclopentadienyl compounds, namely PMC79, PMC78, LCR134 and LCR220, in two CRC-derived cell lines (SW480 and RKO). Biological assays were performed on these CRC cell lines to evaluate cellular distribution, colony formation, cell cycle, proliferation, apoptosis, and motility, as well as cytoskeleton and mitochondrial alterations. Our results show that all the compounds displayed high bioactivity and selectivity, as shown by low half-maximal inhibitory concentrations (IC50) against CRC cells. We observed that all the Ru compounds have different intracellular distributions. In addition, they inhibit to a high extent the proliferation of CRC cells by decreasing clonogenic ability and inducing cell cycle arrest. PMC79, LCR134, and LCR220 also induce apoptosis, increase the levels of reactive oxygen species, lead to mitochondrial dysfunction, induce actin cytoskeleton alterations, and inhibit cellular motility. A proteomic study revealed that these compounds cause modifications in several cellular proteins associated with the phenotypic alterations observed. Overall, we demonstrate that Ru compounds, especially PMC79 and LCR220, display promising anticancer activity in CRC cells with a high potential to be used as new metallodrugs for CRC therapy. Show less
Zhang, Zhao, Wang, Ya-Jun, Wu, Qiong +5 more · 2015 · Australian Journal of Chemistry
Zhang, Zhao, Wang, Ya-Jun, Wu, Qiong, Wu, Xiao-Hui, Sun, Fu-Qiang, Wang, Bao-Guo, Mei, Wen-Jie, Chen, Si-Dong Show less
Mavrynsky, Denys, Rahkila, Jani, Bandarra, Daniel +7 more · 2013 · Organometallics
Mavrynsky, Denys, Rahkila, Jani, Bandarra, Daniel, Martins, Soraia, Meireles, Margarida, Calhorda, Maria José, Kovács, Ida J., Zupkó, István, Hänninen, Mikko M., Leino, Reko Show less
Fontana, Gianfranco, Abbate, Michele, Casella, Girolamo +3 more · 2011 · Polyhedron
Fontana, Gianfranco, Abbate, Michele, Casella, Girolamo, Pellerito, Claudia, Longo, Alessandro, Ferrante, Francesco Show less
Montel, Aline Monezi, dos Santos, Raquel Gouvêa, da Costa, Pryscila Rodrigues +3 more · 2017 · BioMetals
Montel, Aline Monezi, dos Santos, Raquel Gouvêa, da Costa, Pryscila Rodrigues, Silveira-Lacerda, Elisângela de Paula, Batista, Alzir Azevedo, dos Santos, Wagner Gouvêa Show less
Novel metal complexes have received great attention in the last decades due to their potential anticancer activity. Notably, ruthenium-based complexes have emerged as good alternative to the currently Show more
Novel metal complexes have received great attention in the last decades due to their potential anticancer activity. Notably, ruthenium-based complexes have emerged as good alternative to the currently used platinum-based drugs for cancer therapy, providing less toxicity and side effects to patients. Glioblastoma is an aggressive and invasive type of brain tumor and despite of advances is the field of neurooncology there is no effective treatment until now. Therefore, we sought to investigate the potential antiproliferative activity of phosphine-ruthenium-based complexes on human glioblastoma cell lines. Due to its octahedral structure as opposed to the square-planar geometry of platinum(II) compounds, ruthenium(II) complexes exhibit different structure-function relationship probably acting through a different mechanism from that of cisplatin beyond their ability to bind DNA. To better improve the pharmacological activity of metal complexes we hypothesized that neutron activation of ruthenium in the complexes would allow to decrease the effective concentration of the compound needed to kill tumor cells. Herein we report on the effect of unmodified and neutron activated phosphine ruthenium II complexes on glioblastoma cell lines carrying wild-type and mutated p53 tumor suppressor gene. Induction of apoptosis/authophagy as well as generation of reactive oxygen species were determined. The phosphine ruthenium II complexes tested were highly active against glioblastoma cell lines inducing cell death both through apoptosis and autophagy in a p53 independent fashion. Neutron activation of ruthenium compounds rendered them more active than their original counterparts suggesting a new strategy to improve the antitumor activity of these compounds. Show less
Anitha, Panneerselvam, Viswanathamurthi, Periasamy, Misini, Bashkim +1 more · 2013 · Monatshefte für Chemie - Chemical Monthly
Anitha, Panneerselvam, Viswanathamurthi, Periasamy, Misini, Bashkim, Linert, Wolfgang Show less
Radulovic, S., Apostoli, P., Leone, R. +6 more · 2006 · Medicinal Chemistry
Radulovic, S., Apostoli, P., Leone, R., Zunino, F., Perego, P., Gatti, L., Carenini, N., Tesic, Z., Arandjelovic, S. Show less
The aim of this study was to investigate cellular response to several ruthenium(III), chromium(III) and rhodium(III) compounds carrying bidentate beta-diketonato ligands: [(acac)--acetylacetonate liga Show more
The aim of this study was to investigate cellular response to several ruthenium(III), chromium(III) and rhodium(III) compounds carrying bidentate beta-diketonato ligands: [(acac)--acetylacetonate ligand, (tfac)--trifluoroacetylacetonate ligand]. Cell sensitivity studies were performed on several cell lines (A2780, cisplatin-sensitive and -resistant U2-OS and U2-OS/Pt, HeLa, B16) using growth-inhibition assay. Effect of intracellular GSH depletion on cell sensitivity to the agents was analyzed in A2780 cells. Flow cytometry was used to assess apoptosis by Annexin-V-FITC/PI staining, and to analyze induction of caspase-3 activity. Possible DNA binding/damaging affinity was investigated, by inductively coupled mass spectrometry, and by 14C-thymidine / 3H-uridine incorporation assay. Cell sensitivity studies showed that the pattern of sensitivity to Ru(tfac)3 complex of the two cisplatin-sensitive/-resistant osteosarcoma cell lines, U2-OS and U2-OS/Pt, was similar to that of A2780 cells (72 h exposure), with the IC50 being around 40 microM. The growth-inhibitory effect of Ru(acac)3 ranged over 100 microM, while Cr(III) and Rh(III) complexes were completely devoid of antitumor action in vitro. Ru(tfac)3 exhibited strong potential for apoptosis induction on A2780 cells (up to 40%) and caused cell cycle arrest in the S phase as well as decrease of the percent of G1 and G2 cells. Ru(acac)3-induced apoptosis was slightly higher than 10%, whereas activation of caspase-3 in HeLa cells was moderate. DNA binding study revealed that only Cr(acac)3 was capable of binding DNA, while Cr(III) and Ru(III) compounds possess potential to inhibit DNA/RNA synthesis. In conclusion, only Ru(III) complexes showed potential for antitumor action. Show less
Yang, Qingyuan, Zhang, Zhao, Mei, Wenjie +1 more · 2014 · Journal of Chemotherapy
Yang, Qingyuan, Zhang, Zhao, Mei, Wenjie, Sun, Fenyong Show less
Ruthenium complexes are widely recognized as one of the most promising DNA damaging chemotherapeutic drugs. The main goal of this study was to explore the anticancer activity and underlying mechanisms Show more
Ruthenium complexes are widely recognized as one of the most promising DNA damaging chemotherapeutic drugs. The main goal of this study was to explore the anticancer activity and underlying mechanisms of [Ru(phen)(2)(p-BrPIP)](ClO(4))(2), a novel chemically synthesized ruthenium (Ru) complex. To this end, we employed MTT assays to determine the anticancer activity of the complex, and performed single-cell gel electrophoresis (SCGE) and Western blotting to evaluate DNA damage. Our results showed that the Ru(II)-poly complex caused severe DNA damage, possibly by downregulating key factors involved in DNA repair pathways, such as proliferating cell nuclear antigen (PCNA) and ring finger protein 8 (RNF8). In addition, this complex induced cell apoptosis by upregulating both p21 and p53. Taken together, our findings demonstrate that the Ru(II)-poly complex exhibits antitumour activity by inducing cell apoptosis, which results from the accumulation of large amounts of unrepaired DNA damage. Show less
Wise, Dan E., Gamble, Aimee J., Arkawazi, Sham W. +9 more · 2020 · Dalton Transactions
Wise, Dan E., Gamble, Aimee J., Arkawazi, Sham W., Walton, Paul H., Galan, M. Carmen, O'Hagan, Michael P., Hogg, Karen G., Marrison, Joanne L., O'Toole, Peter J., Sparkes, Hazel A., Lynam, Jason M., Pringle, Paul G. Show less
We report cytotoxic ruthenium(ii) complexes of the general formula [RuCl(cis-tach)(diphosphine)]+ (cis-tach = cis-cis-1,3,5-triaminocyclohexane) that have been characterised by 1H, 13C and 31P{1H} NMR Show more
We report cytotoxic ruthenium(ii) complexes of the general formula [RuCl(cis-tach)(diphosphine)]+ (cis-tach = cis-cis-1,3,5-triaminocyclohexane) that have been characterised by 1H, 13C and 31P{1H} NMR spectroscopy, mass spectrometry, X-ray crystallography and elemental analysis. The kinetics of aquation and stability of the active species have been studied, showing that the chlorido ligand is substituted by water at 298 K with first order rate constants of 10-2-10-3 s-1, ideal for potential clinical use as anti-tumour agents. Strong interactions with biologically relevant duplex and quadruplex DNA models correlate with the activity observed with A549, A2780 and 293T cell lines, and the degree of activity was found to be sensitive to the chelating diphosphine ligand. A label-free ptychographic cell imaging technique recorded cell death processes over 4 days. The Ru(ii) cis-tach diphosphine complexes exhibit anti-proliferative effects, in some cases outperforming cisplatin and other cytotoxic ruthenium complexes. Show less
Devi, R. Suganthi, Kumaraguru, N. · 2020 · Asian Journal of Chemistry
Li, Wei, Han, Bing-Jie, Wang, Ji +5 more · 2014 · Inorganica Chimica Acta
Li, Wei, Han, Bing-Jie, Wang, Ji, Jiang, Guang-Bin, Xie, Yang-Yin, Lin, Gan-Jian, Huang, Hong-Liang, Liu, Yun-Jun Show less
Liu, Xue-Wen, Liu, Ning-Yi, Deng, Yuan-Qing +5 more · 2020 · Journal of Radiation Research and Applied Sciences
Liu, Xue-Wen, Liu, Ning-Yi, Deng, Yuan-Qing, Wang, Shan, Liu, Ting, Tang, Yu-Cai, Chen, Yuan-Dao, Lu, Ji-Lin Show less
Liu, Xue-Wen, Ma, Liang, He, Geng-Jun +3 more · 2024 · Journal of Molecular Structure
Liu, Xue-Wen, Ma, Liang, He, Geng-Jun, Hu, Xia, Chen, Yuan-Dao, Zhang, Song-Bai Show less
Lv, Mengdi, Zheng, Yue, Dai, Xiangyu +9 more · 2024 · Journal of Medicinal Chemistry
Lv, Mengdi, Zheng, Yue, Dai, Xiangyu, Zhao, Jingyue, Hu, Guojing, Ren, Meng, Shen, Zhengqi, Su, Zhi, Wu, Chao, Liu, Hong-Ke, Xue, Xuling, Mao, Zong-Wan Show less
Chemoresistance remains an arduous challenge in oncology, but ferroptosis shows potential for overcoming it by stimulating the immune system. Herein, a novel high-performance ruthenium(II)-based arene Show more
Chemoresistance remains an arduous challenge in oncology, but ferroptosis shows potential for overcoming it by stimulating the immune system. Herein, a novel high-performance ruthenium(II)-based arene complex [Ru(η6-p-cym)(BTBpy)Cl] (RuBTB) is developed for ferroptosis-enhanced antitumor immunity and drug resistance reversal via glutathione (GSH) metabolism imbalance. RuBTB shows significantly enhanced antiproliferation activity against cisplatin (CDDP)-resistant lung cancer cells (A549R), with 26.35-fold better anticancer effects than CDDP. Immunogenic ferroptosis is induced by GSH depletion/glutathione peroxidase 4 (GPX4) inactivation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in RuBTB-treated cells. Mechanism studies indicate that RuBTB regulates ferroptosis and immune-related pathways, coordinating with GSH metabolism-mediated glutathione S-transferase (GST) inhibition to reverse drug resistance in platinum-combined therapy. Tumor vaccination experiments demonstrate the intensified antitumor effects endowed by highly immunogenic ferroptosis in vivo. This study provides the first example of a metal-arene complex for achieving satisfactory ferroptosis therapeutic effects with efficient immunogenicity to overcome drug resistance in metal-based immunochemotherapy. Show less
Shadap, Lathewdeipor, Soh, Charlestine, Suting, Smarling +10 more · 2025 · Transition Metal Chemistry
Shadap, Lathewdeipor, Soh, Charlestine, Suting, Smarling, Bhattacharyya, Mayuri, Mylliemngap, Baphilinia Jones, Majaw, Suktilang, Kaminsky, Werner, Umdor, Kenneth, Masharing, Cheerfulman, Laloo, Badaker M., Wahlang, Barisha, Shadap, Matbiangthew, Rymmai, Evergreen K. Show less
Restrepo-Acevedo, Andrés, Murillo, María Isabel, Orvain, Christophe +7 more · 2025 · Inorganic Chemistry
Restrepo-Acevedo, Andrés, Murillo, María Isabel, Orvain, Christophe, Thibaudeau, Chloé, Recberlik, Sevda, Verget, Lucas, Gómez Vidales, Virginia, Gaiddon, Christian, Mellitzer, Georg, Le Lagadec, Ronan Show less
In recent years, photodynamic therapy (PDT) has emerged as a promising alternative to classical chemotherapy for treating cancer. PDT is based on a nontoxic prodrug called photosensitizer (PS) activat Show more
In recent years, photodynamic therapy (PDT) has emerged as a promising alternative to classical chemotherapy for treating cancer. PDT is based on a nontoxic prodrug called photosensitizer (PS) activated by light at the desired location. Upon irradiation, the PS reacts with the oxygen present in the tumor, producing cytotoxic reactive oxygen species (ROS). Compounds with highly conjugated π-bond systems, such as porphyrins and chlorins, have proven to be excellent light scavengers, and introducing a metal atom in their structure improved the generation of ROS. In this work, a series of tetrapyrrole-ruthenium(II) complexes derived from protoporphyrin IX and the commercial drug verteporfin were designed as photosensitizers for PDT. The complexes were almost nontoxic on human gastric cancer cells under dark conditions, revealing remarkable cytotoxicity upon irradiation with light. The ruthenium atom in the central cavity of the chlorin ligand allowed combined mechanisms in photodynamic therapy, as both singlet oxygen and superoxide radicals were detected. Additionally, one complex produced large amounts of singlet oxygen under hypoxic conditions. Biological assays demonstrated that the ruthenium derivatives caused cell death through a caspase 3 mediated apoptotic pathway and via CHOP, an endoplasmic reticulum stress-inducible transcription factor involved in apoptosis and growth arrest. Show less
James, Steffan D., Elgar, Christopher E., Chen, Dandan +8 more · 2024 · Dalton Transactions
James, Steffan D., Elgar, Christopher E., Chen, Dandan, Lewis, Matthew I., Ash, Elias T. L., Conway, Dominic S., Tuckley, Benjamin J., Phillips, Leigh E., Kolozsvári, Natália, Tian, Xiaohe, Gill, Martin R. Show less
Title: Cyrene™ as a green alternative to
Abstract: Ruthenium(II) polypyridyl complexes (RPCs) that emit from triplet metal-to-ligand charge transfer (MLCT) states find a wide variety of uses ranging Show more
Title: Cyrene™ as a green alternative to
Abstract: Ruthenium(II) polypyridyl complexes (RPCs) that emit from triplet metal-to-ligand charge transfer (MLCT) states find a wide variety of uses ranging from luminophores to potential anti-cancer or anti-bacterial therapeutics. Herein we describe a greener, microwave-assisted synthetic pathway for the preparation of homoleptic [Ru(N^N)3]2+ and bis-heteroleptic [Ru(N^N)2(N'^N')]2+ type complexes. This employs the bio-renewable solvent Cyrene™, dihydrolevoglucosenone, as a green alternative to N,N'-dimethylformamide (DMF) in the synthesis of Ru(N^N)2Cl2 intermediate complexes, obtaining comparable yields for N^N = 2,2'-bipyridine, 1,10-phenanthroline and methylated derivatives. Employing these intermediates, a range of RPCs were prepared and we verify that the ubiquitous luminophore [Ru(bpy)3]2+ (bpy = 2,2'-bipyridine) can be prepared by this two-step green pathway where it is virtually indistinguishable from a commercial reference. Furthermore, the novel complexes [Ru(bpy)2(10,11-dmdppz)]2+ (10,11-dmdppz = 10,11-dimethyl-dipyridophenazine) and [Ru(5,5'-dmbpy)2(10,11-dmdppz)]2+ (5,5'-dmbpy = 5,5'-dimethyl-bpy) intercalate duplex DNA with high affinity (DNA binding constants, Kb = 5.7 × 107 and 1.0 × 107 M-1, respectively) and function as plasma membrane and nuclear DNA dyes for confocal and STED microscopies courtesy of their long-lived MLCT luminescence. Show less
Gouveia Júnior, Florêncio S., de Sousa, Allandeiverson S., da Silva, Renally B. +9 more · 2024 · European Journal of Inorganic Chemistry
Gouveia Júnior, Florêncio S., de Sousa, Allandeiverson S., da Silva, Renally B., Rocha, Danilo G., Teixeira, Edson H., Odorico de Moraes Filho, Manoel, Jamacaru, Francisco Vagnaldo F., Serra Azul Monteiro, Helena, Jorge, Roberta Jeane B., Wink, David A., de Sousa, Eduardo Henrique S., de F. Lopes, Luiz Gonzaga Show less
Zhou, Ying, Xiong, Kai, Feng, Tao +4 more · 2025 · Angewandte Chemie International Edition
Zhou, Ying, Xiong, Kai, Feng, Tao, Wu, Xianbo, Liang, Jinzhe, Chen, Yu, Chao, Hui Show less
AbstractOne of the conventional ways to eradicate tumor cells is to utilize chemotherapy agents, e.g., cisplatin, to induce DNA damage. However, DNA damage repair mechanisms can significantly limit th Show more
AbstractOne of the conventional ways to eradicate tumor cells is to utilize chemotherapy agents, e.g., cisplatin, to induce DNA damage. However, DNA damage repair mechanisms can significantly limit the therapeutic efficacy of cisplatin. These mechanisms enable tumor cells to repair the DNA damage caused by the drug, leading to resistance. Cisplatin and similar drugs bind to specific DNA sites without significantly altering their conformation. As a result, DNA repair enzymes can still attach to and repair the damaged DNA. To address this issue, we designed four Ru(II) complexes (RuC3, RuC6, RuC9, and RuC12) with high positive charges of +8 valence and regulated their nuclear accumulation levels by adjusting the length of alkyl chains. RuC9 exhibits the highest nucleus accumulation level. DNA conformation was significantly altered by inducing DNA condensation through indiscriminately neutralizing the negative charge of the DNA backbone. This significant change prevents DNA‐related enzymes from binding to DNA, ultimately leading to the efficient eradication of various tumor cell lines. To the best of our knowledge, it is the first work that kills tumor cells and overcomes cisplatin resistance through inducing DNA condensation. Show less
Ywaya, David O., Ibrahim, Halliru, Friedrich, Holger B. +4 more · 2024 · Molecules
Ywaya, David O., Ibrahim, Halliru, Friedrich, Holger B., Bala, Muhammad D., Soobramoney, Lynette, Daniels, Aliscia, Singh, Moganavelli Show less
A series of new chelating bidentate (SS) alkylimidazole-2-thione-Ru(II)/Os(II) complexes (3ai, 3aii, 3aiii, 3bii/4aiiiShow more
A series of new chelating bidentate (SS) alkylimidazole-2-thione-Ru(II)/Os(II) complexes (3ai, 3aii, 3aiii, 3bii/4aiii, 4bi, 4bii), and the tridentate (SNS) pyridine-2,6-diylimidazole-2-thione-Ru(II)/Os(II) complexes (5bi, 5civ/6bi, 6ci, 6civ) in the forms [MII(cym)(L)Cl]PF6 and [MII(cym)(L)]PF6 (M = Ru or Os, cym = η6-p-cymene, and L = heterocyclic derivatives of thiourea) respectively, were successfully synthesized. Spectroscopic and analytical methods were used to characterize the complexes and their ligands. Solid-state single-crystal X-ray diffraction analyses revealed a "piano-stool" geometry around the Ru(II) or Os(II) centers in the respective complexes. The complexes were investigated for in vitro chemotherapeutic activities against human cervical carcinoma (HeLa) and the non-cancerous cell line (Hek293) using the MTT assay. The compounds 3aii, 5civ, 5bi, 4aiii, 6ci, 6civ, and the reference drug, 5-fluorouracil were found to be selective toward the tumor cells; the compounds 3ai, 3aiii, 3bii, 4bi, 4bii, and 6bi, which were found not to be selective between normal and tumor cell lines. The IC50 value of the tridentate half-sandwich complex 5bi (86 ± 9 μM) showed comparable anti-proliferative activity with the referenced commercial anti-cancer drug, 5-fluorouracil (87 ± 15 μM). The pincer (SNS) osmium complexes 6ci (36 ± 10 μM) and 6civ (40 ± 4 μM) were twice as effective as the reference drug 5-fluorouracil at the respective dose concentrations. However, the analogous pincer (SNS) ruthenium complex 5civ was ineffective and did not show anti-proliferative activity, even at a higher concentration of 147 ± 1 μM. These findings imply that the higher stability of the chelating (SS) and the pincer (SNS) ligand architectures in the complexes improves the biological (anti-proliferative) activity of the complexes by reducing the chance of ligand dissociation under physiological conditions. In general, the pincer (SNS) osmium complexes were found to be more cytotoxic than their ruthenium analogues, suggesting that the anti-proliferative activity of the imidazole-2-thione-Ru/Os complexes depends on the ligand's spatial coordination, the nature of the metal center, and the charge of the metal complex ions. Show less
Khalifa, Amr, Sheweita, Salah, Namatalla, Asmaa +3 more · 2025 · Cancers
Khalifa, Amr, Sheweita, Salah, Namatalla, Asmaa, Khalifa, Mohamed, Nencioni, Alessio, Sultan, Ahmed Show less
Background/objectives
Breast cancer (BC) remains one of the most prevalent and deadly cancers worldwide, with limited access to advanced treatments in developing regions. There is a critical n Show more
Background/objectives
Breast cancer (BC) remains one of the most prevalent and deadly cancers worldwide, with limited access to advanced treatments in developing regions. There is a critical need for novel therapies with unique mechanisms of action, especially to overcome resistance to conventional platinum-based drugs. This study investigates the anticancer potential of the ruthenium complex Bis(quinolin-8-olato)bis(triphenylphosphine)ruthenium(II) (Ru(quin)2) in ER-positive (T47D) and triple-negative (MDA-MB-231) BC cell lines.Results
Ru(quin)2 demonstrated dose-dependent cytotoxicity, with IC50 values of 48.3 μM in T47D cells and 45.5 μM in MDA-MB-231 cells. Its cytotoxic effects are primarily driven by apoptosis, as shown by increased BAX expression, enhanced caspase-3 activity, reduced Aurora B kinase levels, and elevated histone release. Ru(quin)2 also induced autophagy, evidenced by LC3-I to LC3-II conversion and reduced SQSTM1, partially mediated through MAPK signaling. Furthermore, Ru(quin)2 induced G0/G1 cell cycle arrest by downregulating cyclin D1, CDK4, and CDK6, alongside upregulation of the CDK inhibitor p21.Conclusions
Ru(quin)2 emerges as a potent candidate for BC treatment, with multiple mechanisms of action involving apoptosis, autophagy, and cell cycle arrest. Further studies are warranted to elucidate its detailed molecular mechanisms and evaluate its therapeutic potential in vivo, moving toward clinical applications for both ER-positive and triple-negative BC management. Show less
Hong, Xian-Lan, Xu, Juan, Jiang, Rong-Hui +3 more · 2020 · Transition Metal Chemistry
Hong, Xian-Lan, Xu, Juan, Jiang, Rong-Hui, Li, Jie-Ying, Chen, Jie-Li, Lu, Fu-Changsheng Show less
Soldevila‐Barreda, Joan J., Pettenuzzo, Andrea, Azmanova, Maria +6 more · 2023 · Helvetica Chimica Acta
Soldevila‐Barreda, Joan J., Pettenuzzo, Andrea, Azmanova, Maria, Rafols, Laia, Attia, Amr A. A., Lupan, Alexandru, Ronconi, Luca, Barry, Nicolas P. E., Pitto‐Barry, Anaïs Show less
Delgado, Ricardo A., Galdámez, Antonio, Tessini, Catherine +5 more · 2020 · Journal of Organometallic Chemistry
Delgado, Ricardo A., Galdámez, Antonio, Tessini, Catherine, Ramírez-Rivera, Sebastián, Aquea, Gisela, Bernal, Giuliano, Pinter, Balazs, Thomet, Franz A. Show less
Dhibar, Papu, Chandra, Anushri, Kundu, Sweta +2 more · 2024 · European Journal of Inorganic Chemistry
Dhibar, Papu, Chandra, Anushri, Kundu, Sweta, Acharya Chowdhury, Avik, Bhattacharya, Samaresh Show less
Barolli, João, Corrêa, Rodrigo, Miranda, Fabio +6 more · 2017 · Journal of the Brazilian Chemical Society
Barolli, João, Corrêa, Rodrigo, Miranda, Fabio, Ribeiro, Juliana, Bloch Jr., Carlos, Ellena, Javier, Moreno, Virtudes, Cominetti, Márcia, Batista, Alzir Show less
Liu, Si-Hong, Xu, Hui-Hua, Zhu, Jian-Wei +8 more · 2016 · Polyhedron
Liu, Si-Hong, Xu, Hui-Hua, Zhu, Jian-Wei, Wang, Yan, Liu, Ya-Min, Liang, Jun-Bo, Zhang, Gui-Qiang, Cao, Di-Hua, Lin, Yang-Yang, Guo, Qi-Feng, Wu, Yong Show less
Peng, Xiaolong, Tang, Qiang, Zhu, Huiyun +3 more · 2023 · Journal of Inorganic Biochemistry
Peng, Xiaolong, Tang, Qiang, Zhu, Huiyun, Bai, Lijuan, Zhao, Hua, Chen, Yongjie Show less
Three ruthenium arene complexes, namely {[(η6-p-cymene)Ru(Cl)]2(dpb)}(PF6)2 (1), [(η6-p-cymene)Ru(dpb)Cl](PF6) (2) and [(η6 Show more
Three ruthenium arene complexes, namely {[(η6-p-cymene)Ru(Cl)]2(dpb)}(PF6)2 (1), [(η6-p-cymene)Ru(dpb)Cl](PF6) (2) and [(η6-p-cymene) Ru(dpb)py](PF6) (3) (dpb = 2,3-bis(2-pyridyl)benzo-quinoxaline, py = pyridine), were synthesized and their antitumor properties were introduced. Complexes 1-3 were characterized by 1H NMR, MS, and elemental analysis. As a binuclear ruthenium structure, the absorption of metal ligand electron transfer (MLCT) of 1 extended to 700 nm. Complex 1 was significantly hydrolyzed under dark conditions. The cytotoxicity in vitro study showed that complexes 1 and 2 are more toxic to human lung cancer cells (A549) and human cervial cancer cells (Hela) than cisplatin. Moreover, there was almost no cross-resistance between complex 1-2 and cisplatin. Under the irradiation at 478 nm, complexes 1-3 all produced singlet oxygen (1O2), and the 1O2 quantum yield of complex 1 in PBS is the highest among complexes 1-3. Complex 1 also produced 1O2 under 600 nm light irradiation. DNA gel electrophoresis showed that 1 caused the photocleavage of plasmid DNA. The hydrolysis rate of complex 1 was accelerated under light (λ > 600 nm). And the phototoxicity of complex 1 to Hela cells under light (λ > 600 nm) was much greater than its dark toxicity, which may be due to its generation of 1O2 and the promotion of its hydrolysis under long-wave light irradiation. Show less