Article
Chemistry, Multidisciplinary
Qi-Yuan Yang, Rui Ma, Yun-Qiong Gu, Xiao-Fang Xu, Zhen-Feng Chen, Hong Liang
Summary: Targeting metabolic reprogramming to treat cancer, by using arene-ruthenium(II)/osmium(II) complexes to potentiate the anticancer effect of metformin (Met.) via glucose metabolism reprogramming, could increase overall survival and reduce side effects.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Inorganic & Nuclear
Thimma Subramanian Prathima, Badruzzaman Choudhury, Md. Gulzar Ahmad, Kaushik Chanda, M. M. Balamurali
Summary: Numerous biologically active metal complexes have been reported for their unique features and enhanced functions in inhibiting cancer progression. However, many of these drugs have failed at various levels of clinical trials despite performing well in the laboratory.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Chemistry, Inorganic & Nuclear
Stefan Latis, Christoph Marschner, Judith Baumgartner, Sharon Prince, Supratim Biswas, Suparna Chakraborty, Kimberly G. Garcia, Ron M. A. Heeren, Sebastiaan Van Nuffel, Burgert Blom
Summary: This study reports the synthesis and characterisation of piano-stool triphenylstibine and triphenylarsine arene complexes, and their in vitro cytotoxic evaluation on breast cancer cell lines. The tin containing complexes demonstrate remarkable activity and selectivity.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Pragti, Sreshtha Nayek, Satyam Singh, Avinash Sonawane, Ivo Grabchev, Rakesh Ganguly, Suman Mukhopadhyay
Summary: In this study, three Ru(II) arene complexes with a bidentate benzimidazole-based ligand were synthesized and their antitumor activity was studied by varying the co-ligand X. The synthesized compounds showed good interactions with serum albumin proteins, had good drug stability and lipophilic character. They were found to bind with DNA and could induce apoptosis in cancer cells, as well as upregulate cleaved caspase-3 expression and downregulate BCLXL expression. These findings provide a new direction for the investigation of antitumor ruthenium-based metallodrugs using benzimidazole-based ligands.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Multidisciplinary
Hau-Lam Shek, Chi-Fung Yeung, Lai-Hon Chung, Man-Kit Tse, Shek-Man Yiu, Chun-Yuen Wong
Summary: Systematic investigation of the reactions between cis-[M(dppm)(2)Cl-2] (M=Ru/Os; dppm=1,1-bis(diphenylphosphino)methane) and pyridine/quinoline substituted homopropargylic alcohols revealed diverse Ru(II)/Os(II)-induced alkyne activation pathways. At lower temperatures, alkynes cyclized on M via a non-vinylidene pathway, forming alkenyl intermediates that further metallacyclized to give metallapyrroloindolizines. Conversely, at higher temperatures, alkyne cyclization on M occurred via a vinylidene pathway, resulting in cyclic oxacarbene complexes. A rare decyclization mechanism was observed during the transformation of a metallacyclization-resistant alkenyl complex into a cyclic oxacarbene complex. DFT calculations confirmed the experimental findings. Overall, these results provide insights into controlling alkyne activation pathways and offer new strategies for preparing metalated heterocyclic and metallacyclic complexes.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Jakob Kljun, Mihaela Rebernik, Lucia M. Balsa, Jerneja Kladnik, Uros Rapus, Tomaz Trobec, Kristina Sepcic, Robert Frangez, Ignacio E. Leon, Iztok Turel
Summary: Organoruthenium pyrithione complexes, such as [(eta(6)-p-cymene)Ru(pyrithionato)(pta)]PF6, show promise as a new class of anticancer drugs. Our study focuses on finding alternatives to the pta ligand and discovering new structural elements to improve the biological properties of ruthenium anticancer drugs. By replacing the pta ligand with different phosphine, phosphite, and arsine ligands, we identified improved inhibitory potency against the enzyme glutathione S-transferase, as well as investigated cytotoxicity in breast, bone, and colon cancers.
Review
Chemistry, Inorganic & Nuclear
Srividya Swaminathan, Rajasekharan Jayakumari Deepak, Ramasamy Karvembu
Summary: The field of bioorganometallic chemistry has seen significant expansion in recent years, particularly in the development of efficient catalysts and anticancer drugs using organometallic complexes. The properties and processes of these complexes, particularly those of ruthenium(II) and osmium(II), rely on electronic and steric factors. These complexes have been widely used as versatile precursors in biological and catalytic applications. By indirectly affecting cellular redox homeostasis through catalytic transfer hydrogenation, they have shown promise in anticancer therapy.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
Srividya Swaminathan, Jebiti Haribabu, Naveen Kumar Kalagatur, Maroli Nikhil, Nithya Balakrishnan, Nattamai S. P. Bhuvanesh, Krishna Kadirvelu, Ponmalai Kolandaivel, Ramasamy Karvembu
Summary: The synthesis of fourteen new Ru-II-arene complexes were characterized and found to exhibit high toxicity towards IMR-32 cancer cells, with two complexes showing the highest activity and the ability to induce apoptosis and cell cycle arrest. These complexes also demonstrated good binding affinity with receptors commonly overexpressed in cancer cells.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Emanuele Zanda, Natalia Busto, Lorenzo Biancalana, Stefano Zacchini, Tarita Biver, Begona Garcia, Fabio Marchetti
Summary: The study found that certain ruthenium complexes exhibited remarkable stability in water and cell culture medium, showing strong cytotoxicity against cancer cell lines, with RUCYN being the most promising one with significant selectivity compared to non-cancerous cells. The variability of affinity of the complexes for BSA and DNA binding was determined, with certain complexes showing enhanced cell internalization and cytotoxicity at the expense of selectivity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Chemistry, Multidisciplinary
Tomiris Nabiyeva, Basile Roufosse, Matylda Odachowski, Judith Baumgartner, Christoph Marschner, Akalesh Kumar Verma, Burgert Blom
Summary: A series of osmium arene complexes involving sigma-germyl, germanate, sigma-stannyl, and stannate ligands were synthesized, characterized, and tested for potential anticancer activities. Comprehensive analyses using various techniques were conducted, along with cytotoxicity and apoptosis assays against malignant cancer cell lines. The study revealed that some of the complexes exhibited anti-cancer effects on malignant cancer cells.
Article
Biochemistry & Molecular Biology
Zahid Riaz, Betty Y. T. Lee, Julia Stjarnhage, Sanam Movassaghi, Tilo Sohnel, Stephen M. F. Jamieson, Muhammad Ashraf Shaheen, Muhammad Hanif, Christian G. Hartinger
Summary: The substitution of the labile chloride ligand with phosphorus donor ligands in half-sandwich MII(cym)Cl complexes showed that Ru and Os complexes with triphenylphosphine ligands exhibited the most potent anticancer activity in submicromolar range against four cancer cell lines. This suggests that the antiproliferative activity is mainly dependent on the lipophilic properties of the phosphine ligand.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Arunachalam Abirami, Umapathy Devan, Rengan Ramesh, Arockiam Antony Joseph Velanganni, Jan Grzegorz Malecki
Summary: This study synthesized six arene ruthenium(ii) complexes and evaluated their inhibitory effects on breast cancer cells. The complexes exhibited good antiproliferative activities by inducing apoptotic cell death through an intrinsic mitochondrial pathway.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Multidisciplinary
Sankar Monika, Rengan Ramesh
Summary: This study reports the synthesis of a new series of organometallic dinuclear ruthenium(ii) arene complexes and investigates their in vitro antiproliferative activity and cancer cell death mechanism. The formation of complexes was confirmed by various spectroscopic techniques. The synthesized complexes showed higher inhibition of cancer cells compared to the standard cisplatin drug, and apoptosis was confirmed through morphological changes and phosphatidylserine externalization.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Brondwyn S. McGhie, Janice R. Aldrich-Wright
Summary: Cancer is responsible for over 9 million deaths worldwide each year. Current treatment options have low success rates, especially for late-stage cancers. Researchers globally are continuously searching for alternative treatment options. This study focuses on innovations in inorganic anticancer therapies with photoactive and luminescent properties. Transition metals offer advantages in both chemotherapeutics and luminescence. The study explores the effects of structural changes on the properties and the use of inherent luminescent properties for monitoring cellular localization in photodynamic therapy.
Article
Chemistry, Inorganic & Nuclear
Sonia Infante-Tadeo, Vanessa Rodriguez-Fanjul, Cintia C. Vequi-Suplicy, Ana M. Pizarro
Summary: The passage describes the rapid hydrolysis and high basicity of complexes [Os(eta 6-arene)(C,N-phenylpyridine)Z] with chlorido or tethered oxygen as the ligand. It also reveals the structure-activity relationship between Os-CN and Os-NN complexes.
INORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sarah J. Farley, Luca Salassa, Ana M. Pizarro, Peter J. Sadler
Summary: Platinum(II) complexes containing N,N-chelating ligand phenylazopyridine have been synthesized and characterized to investigate the effects of monodentate ligands and phenyl substituents on their absorption spectra and photoactivation. The complexes exhibit redshift and photoactivity, with strong contributions from chlorido and azido groups. Further analysis through spectroscopy and theoretical calculations elucidates the mechanism behind their photoactivation.
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Giovanni Salassa, Luca Salassa
Summary: This passage highlights methods developed by coordination and organometallic chemists that surpass mainstream inorganic reactivity. Through transmetalation, metal exchange, metal cooperativity, and catalytic transformation of metal complexes, new opportunities are provided to expand the reactivity arsenal of inorganic systems for synthesis and technological applications.
Article
Chemistry, Physical
Juan Gurruchaga-Pereda, Virginia Martinez-Martinez, Elena Formoso, Oksana Azpitarte, Elixabete Rezabal, Xabier Lopez, Aitziber L. Cortajarena, Luca Salassa
Summary: Our recent research shows that protein engineering can enhance the catalytic capacity of certain flavoproteins towards metal-containing substrates. By using site-directed mutagenesis, the photocatalytic activity of flavoprotein towards Pt(IV) substrates can be modulated. Among the mutants prepared, Q103V mSOG exhibited improved catalytic efficiency due to its longer triplet excited-state lifetime.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Oncology
Jerneja Kladnik, James P. C. Coverdale, Jakob Kljun, Hilke Burmeister, Petra Lippman, Francesca G. Ellis, Alan M. Jones, Ingo Ott, Isolda Romero-Canelon, Iztok Turel
Summary: Ovarian cancer is a common cancer in the developing world, and resistance to platinum-based anticancer agents is a growing concern in treatment. A new family of organoruthenium(II) pyrithione complexes were explored for their efficacy towards platinum-resistant ovarian cancer cells, showing high potency and a unique mechanism of action compared to platinum agents. This study highlights the development of next-generation anticancer agents that can overcome resistance to existing therapies and the potential of transition metal complexes in multi-targeting mechanisms.
Article
Chemistry, Physical
Stefano Scoditti, Eslam Dabbish, German E. Pieslinger, Elixabete Rezabal, Xabier Lopez, Emilia Sicilia, Luca Salassa
Summary: The mechanism for the photocatalytic activation of Pt(iv) anticancer prodrugs by riboflavin in the presence of NADH has been investigated. The results demonstrate that riboflavin accelerates the hydride transfer from NADH to riboflavin in the excited state, and facilitates the reduction of Pt(iv) complexes via an inner sphere mechanism.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Susana Velasco-Lozano, Silvia Alonso-de Castro, Carlos Sanchez-Cano, Ana Benitez-Mateos, Fernando Lopez-Gallego, Luca Salassa
Summary: The research demonstrates that flavin reactivity within a hydrogel matrix can efficiently catalyze the activation and delivery of cisplatin, enhancing substrate conversion rates and enabling controlled drug release through light or chemical stimuli.
Article
Chemistry, Multidisciplinary
Alessio Terenzi, Mery La Franca, Sushilla van Schoonhoven, Rostyslav Panchuk, Alvaro Martinez, Petra Heffeter, Redding Gober, Christine Pirker, Petra Vician, Christian R. Kowol, Rostyslav Stoika, Luca Salassa, Jurgen Rohr, Walter Berger
Summary: Landomycins are angucyclines produced by Streptomyces bacteria, showing promising anti-cancer activity through the formation of Michael adducts with biothiols. These adducts exhibit intense blue fluorescence intracellularly, allowing for label-free tracking and insights into the mechanism of action.
COMMUNICATIONS CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Giovanni Canil, Juan Gurruchaga-Pereda, Simona Braccini, Lorella Marchetti, Tiziana Funaioli, Fabio Marchetti, Alessandro Pratesi, Luca Salassa, Chiara Gabbiani
Summary: Photoactivatable Pt(IV) prodrugs have great potential as metal-based drugs due to their chemical inertness in oxidized form and selective targeting compared to Pt(II) compounds. A new Pt(IV) complex, soluble in water and unreactive until reduction, was synthesized. The complex exhibited rapid and efficient photoreduction with visible light, facilitated by a catalytic system based on flavin and NADH. The reactivity of the prodrug against biological targets was only observed after photoreduction to its Pt(II) analogue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Oksana Azpitarte, Ane Zudaire, Jon Uranga, Xabier Lopez, Luca Salassa, Elena Formoso, Elixabete Rezabal
Summary: The unconventional bioorthogonal catalytic activation of anticancer metal complexes by flavin and flavoproteins photocatalysis has been recently reported. The reactivity is based on a two-electron redox reaction of the photoactivated flavin. In addition, site mutagenesis has been found to modulate and improve the catalytic activity of mini Singlet Oxygen Generator protein (SOG). The redox properties of flavin and the resulting reactivity of miniSOG are modulated by specific mutations, which is consistent with experimental results.
Article
Chemistry, Inorganic & Nuclear
Juan Sanchez-Camacho, Sonia Infante-Tadeo, Ana C. Carrasco, Stefano Scoditti, A'lvaro Martinez, Fabienne Barroso-Bujans, Emilia Sicilia, Ana M. Pizarro, Luca Salassa
Summary: In this study, two new asymmetric Pt(IV) derivatives were designed and synthesized, which could be effectively activated into toxic Pt(II) species by incubation with nicotinamide adenine dinucleotide, sodium ascorbate, and glutathione in the dark and under light irradiation. One of the derivatives displayed enhanced toxicity in MDA-MB-231 breast cancer cells preincubated with ascorbate, suggesting selective triggering of oxaliplatin generation through redox activation. Covalent binding of the flavin to the Pt complex was shown to be pivotal for this effect.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Laura F. Mazzei, Juan Gurruchaga-Pereda, Alvaro Martinez, Javier Calvo Martinez, Luca Salassa, Aitziber L. Cortajarena
Summary: In this study, a multifunctional hybrid was developed for controlling the delivery and activation of Pt anticancer agents in vitro. Consensus tetratricopeptide repeat protein (CTPR) was used to covalently co-anchor riboflavin (photocatalyst) and a Pt(iv) prodrug complex. The Pt-loaded flavoprotein induced a 40% reduction in PANC-1 cell viability through the photocatalytic formation of cisplatin.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Hannah E. Bridgewater, Elizabeth M. Bolitho, Isolda Romero-Canelon, Peter J. Sadler, James P. C. Coverdale
Summary: Synthetic anticancer catalysts offer new approaches to low-dose therapy and targeted treatment of biochemical pathways. To optimize their activity and avoid poisoning, the synthetic organometallic redox catalyst [Os(p-cymene)(TsDPEN)] is combined with the monocarboxylate transporter (MCT) inhibitor AZD3965, which significantly increases its activity in MCF7 breast cancer cells. AZD3965 also decreases glutathione levels and enhances mitochondrial metabolism, providing a novel strategy for low-dose combination therapy.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Marium Rana, Alessio Perotti, Lucy M. Bisset, James D. Smith, Emma Lamden, Zahra Khan, Media K. Ismail, Katherine Ellis, Katie A. Armstrong, Samantha L. Hodder, Cosetta Bertoli, Leticia Meneguello, Robertus A. M. de Bruin, Joanna R. Morris, Isolda Romero-Canelon, James H. R. Tucker, Nikolas J. Hodges
Summary: In this study, a new nucleoside analogue, 1-(S,R-p), was found to be cytotoxic to gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cells, by inhibiting DNA replication and arresting cell cycle at S-phase, as observed directly through DNA-fibre fluorography. Moreover, the compound was shown to activate several genes and downstream targets related to DNA replication and cell cycle regulation. These findings suggest that 1-(S,R-p) can be a promising candidate for the development of new treatments for PDAC.
Article
Chemistry, Inorganic & Nuclear
Feng Chen, Isolda Romero-Canelon, Abraha Habtemariam, Ji-Inn Song, Samya Banerjee, Guy J. Clarkson, Lijiang Song, Ivan Prokes, Peter J. Sadler
Summary: We synthesized a series of novel substituted sulfonyl ethylenediamine (en) Ru-II arene complexes, which showed antiproliferative activity against cancer cells and exhibited catalytic activity in transfer hydrogenation reactions and reactions with thiols.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Inorganic & Nuclear
Evyenia Shaili, Maria J. Romero, Luca Salassa, Julie A. Woods, Jennifer S. Butler, Isolda Romero-Canelon, Guy Clarkson, Abraha Habtemariam, Peter J. Sadler, Nicola J. Farrer
Summary: The synthesis and characterization of four platinum complexes were conducted and analyzed using various methods. Complexes 1-3 demonstrated phototoxicity under green light irradiation, with complexes 1 and 2 exhibiting higher photocytotoxicity and activity against cisplatin-resistant cell lines.
DALTON TRANSACTIONS
(2021)