Article
Chemistry, Inorganic & Nuclear
Srividya Swaminathan, Jebiti Haribabu, Mahendiran Dharmasivam, Nikhil Maroli, Jayachandra Prakasan Jayadharini, Nithya Balakrishnan, Nattamai Bhuvanesh, Cesar Echeverria, Ramasamy Karvembu
Summary: We designed and synthesized bipodal ligands with varying substitution on the phenyl group spacer. Ligands and complexes with different arene units were successfully synthesized and characterized. The coordination behavior of the ligands was minimally influenced by substitution change, but differences were observed in the anticancer activity of the complexes. DFT and X-ray diffraction studies revealed structural variations between the different substitutions, and UV-visible spectroscopy determined the correlation between anticancer activity, hydrolysis rate, and lipophilicity index of the complexes. Staining assays, flow cytometry, and Western blot analysis confirmed the apoptotic cell death mechanism of the active complexes.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Kelvin K. H. Tong, Mie Riisom, Euphemia Leung, Muhammad Hanif, Tilo Sohnel, Stephen M. F. Jamieson, Christian G. Hartinger
Summary: In this study, organometallic complexes with a piano-stool structure and di- or tridentate ligand systems were reported, showing improved biological activity and impact on cytotoxic activity.
INORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alice De Palo, Dijana Draca, Maria Grazia Murrali, Stefano Zacchini, Guido Pampaloni, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Fabio Marchetti
Summary: Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand have been extensively studied as potential anticancer drugs, with two complexes showing significant antiproliferative activity on multiple cancer cell lines. These complexes do not affect the viability of primary mouse peritoneal cells and exert their tumoricidal effects through a combination of effects on cellular proliferation, apoptosis, and senescence triggered by mitochondrial failure and reactive oxygen and nitrogen species production.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Inorganic & Nuclear
Riccardo Pettinari, Fabio Marchetti, Alessia Tombesi, Corrado Di Nicola, Claudio Pettinari, Chuanpan Guo, Zhihong Zhang, Agustin Galindo, Farzaneh Fadaei-Tirani, Mouna Hadiji, Paul J. Dyson
Summary: Two new pyrazole ligands with a pyridine moiety were synthesized and fully characterized, and their coordination modes in metal complexes were analyzed. Cytotoxicity studies showed similar activity of these ligands and complexes in cisplatin-sensitive and cisplatin-resistant ovarian carcinoma cells.
INORGANICA CHIMICA ACTA
(2021)
Article
Chemistry, Inorganic & Nuclear
Raphael Lengacher, Henrik Braband, Joshua Csucker, Roger Alberto
Summary: This article describes the synthesis of a novel bifunctional cyclopentadiene-based building block and its corresponding derivatives, which can be prepared through a simple nucleophilic substitution reaction. This building block can be used to prepare new drug candidates for brain imaging and multi-drug resistance in cancer, while demonstrating its versatility in Click-type reactions.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Malgorzata Fabijanska, Maria M. Kasprzak, Justyn Ochocki
Summary: The study found that ruthenium compounds can partially or completely overcome the resistance to platinum drugs by activating apoptosis pathways and inducing loss of mitochondrial membrane potential, while platinum compounds have cytostatic effects requiring longer exposure time. Additionally, cisplatin-resistant cells have higher glutathione levels compared to sensitive cells, indicating mechanisms to evade apoptosis caused by DNA damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Dat Nguyen, Guangjie Yan, Tai-Yen Chen, Loi H. Do
Summary: Studies using single-molecule fluorescence microscopy have revealed that allylcarbamate cleavage reactions promoted by Ru complexes occur more frequently inside mitochondria than in non-mitochondrial regions in live A549 human lung cells. The turnover frequency of the Ru complexes was at least 3-fold higher in mitochondria. These findings highlight the importance of organelle specificity in the design of intracellular catalysts for therapeutic applications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Inorganic & Nuclear
Betty Y. T. Lee, Matthew P. Sullivan, Ena Yano, Kelvin K. H. Tong, Muhammad Hanif, Tomoyo Kawakubo-Yasukochi, Stephen M. F. Jamieson, Tilo Soehnel, David C. Goldstone, Christian G. Hartinger
Summary: N-Heterocyclic carbene (NHC) ligands have been widely studied in medicinal inorganic chemistry. In this study, a series of half-sandwich [M(L)(NHC)Cl-2] complexes with N-flanking anthracenyl moiety were prepared and their anticancer activities were investigated, showing cytotoxicity in low micromolar range. The Ru derivative 1a exhibited stability and specific interactions with biomolecules.
INORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anita Raducka, Marcin Swiatkowski, Izabela Korona-Glowniak, Barbara Kapron, Tomasz Plech, Malgorzata Szczesio, Katarzyna Gobis, Malgorzata Iwona Szynkowska-Jozwik, Agnieszka Czylkowska
Summary: In this study, a series of coordination compounds containing zinc and benzimidazole derivatives were synthesized and characterized using various analytical and spectroscopic techniques. The results indicated that these new compounds showed improved anticancer properties, as well as antibacterial and antifungal activities, demonstrating potential as antitumor agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Ana R. Rubio, Rocio Gonzalez, Natalia Busto, Monica Vaquero, Ana L. Iglesias, Felix A. Jalon, Gustavo Espino, Ana M. Rodriguez, Begona Garcia, Blanca R. Manzano
Summary: In the field of anticancer chemotherapy, a study has been conducted to synthesize metal complexes with bioactive ligands to overcome drug resistance. The results show that one of the complexes has high cytotoxicity, induces apoptosis, overcomes drug resistance, and displays selectivity towards cancer cells through DNA binding and ROS generation pathways.
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
Chemistry, Inorganic & Nuclear
Luis Felipe Hernandez-Ayala, Cynthia Sinai Novoa-Ramirez, Miguel Reina, Lena Ruiz-Azuara
Summary: This study presents the synthesis, characterization, electrochemical studies, DFT calculations, and in vitro evaluation of four novel direct bonded ruthenium-selenium compounds, revealing the impact of intermediate properties and compound structure on cytotoxic activity, with 2c demonstrating the best inhibitory effect on cell proliferation.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Shuhua Cao, Anlin Wang, Kaoxue Li, Zhiteng Lin, Hongwei Yang, Xiaolei Zhang, Jianmei Qiu, Xishi Tai
Summary: A novel tetranuclear Cu(ii) complex (TNC) was synthesized and characterized by X-ray single crystal diffraction. The interaction with calf thymus DNA (CT-DNA) was investigated and it was found that TNC can bind to the DNA through an intercalative mode. The anticancer activity of TNC was tested on four cancer cell lines and showed significant activity against all of them.
Article
Chemistry, Multidisciplinary
Benjamin Neuditschko, Anton A. Legin, Dina Baier, Arno Schintlmeister, Siegfried Reipert, Michael Wagner, Bernhard K. Keppler, Walter Berger, Samuel M. Meier-Menches, Christopher Gerner
Summary: The study reveals that the anticancer agent BOLD-100 interacts with ribosomal proteins, induces ER stress, and modulates GRP78 in cancer cells. Target-profiling experiments and cellular observations provide evidence for these changes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
Efres Belmonte-Reche, Alessandra Benassi, Pablo Penalver, Anne Cucchiarini, Aurore Guedin, Jean Louis Mergny, Frederic Rosu, Valerie Gabelica, Mauro Freccero, Filippo Doria, Juan Carlos Morales
Summary: Glycosyl conjugation to drugs is a strategy that takes advantage of the overexpression of glucose transporters (GLUT) in cancer cells to achieve targeted therapy. In this study, a series of thiosugar naphthalene diimide conjugates were synthesized and the effects of modifications to the amino sidechain on their antiproliferative activity, antiparasitic activity, ability to bind quadruplexes, cellular uptake, and location were investigated.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Valentin Fuchs, Klaudia Cseh, Michaela Hejl, Petra Vician, Benjamin Neuditschko, Samuel M. Meier-Menches, Lukas Janker, Andrea Bileck, Natalie Gajic, Julia Kronberger, Martin Schaier, Sophie Neumayer, Gunda Koellensperger, Christopher Gerner, Walter Berger, Michael A. Jakupec, Michael S. Malarek, Bernhard K. Keppler
Summary: A series of highly lipophilic Cp-substituted molybdenocenes with different bioactive chelating ligands were synthesized and characterized. They showed significantly increased cytotoxic potency compared to non-Cp-substituted counterparts. In vivo experiments demonstrated tumor growth inhibition for the most active complex containing the thioflavone ligand, along with significant regulation of tubulin-associated and mitochondrial inner membrane proteins.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Janos P. Meszaros, Wolfgang Kandioller, Gabriella Spengler, Alexander Prado-Roller, Bernhard K. Keppler, Eva A. Enyedy
Summary: This study introduces half-sandwich Rh complexes that can be activated in the acidic, extracellular pH of tumor tissue, reducing the side effects and improving the efficacy of chemotherapy.
Review
Biochemistry & Molecular Biology
Yasmin Borutzki, Lukas Skos, Christopher Gerner, Samuel M. Meier-Menches
Summary: In recent years, metal-based candidate drugs have shown promise as modulators of cytoskeletal and cytoskeleton-associated proteins. Actin, vimentin, and plectin have been identified as targets of ruthenium(II) and platinum(II)-based modulators. However, there is limited structural information available on molecular interactions. This article compiles scattered reports on metal-based candidate molecules influencing the cytoskeleton and its associated proteins, exploring their potential in cancer-related processes.
Article
Chemistry, Multidisciplinary
Karolina Kowalczyk, Andrzej Blauz, Daniel Moscoh Ayine-Tora, Christian G. Hartinger, Blazej Rychlik, Damian Plazuk
Summary: Derivatives of ispinesib and its (S) analogue, containing ferrocenyl moieties or bulky organic substituents, were prepared to combine multiple biologically-active components in a single molecule. Several of these compounds demonstrated higher antiproliferative activity than ispinesib, with nanomolar IC50 values against cell lines. The improved activity may be attributed to synergic effects of various factors such as KSP inhibitory activity due to the ispinesib core and ability to generate ROS and induce mitotic arrest.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Lukas Skos, Yasmin Borutzki, Christopher Gerner, Samuel M. Meier-Menches
Summary: Metal-based anticancer agents occupy a unique chemical space and can be tuned to target proteins as well as DNA. Tailored proteomics strategies are crucial for identifying and validating protein targets of metal-based drugs. Experimental approaches discussed in this article have shown that metals such as ruthenium, gold, rhenium, and platinum can selectively target proteins with downstream effects. Target identification strategies are expected to greatly support the clinical translation of metal-based drugs.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
William D. J. Tremlett, Tilo Soehnel, James D. Crowley, L. James Wright, Christian G. Hartinger
Summary: Using ferrocene-based ligand systems, a series of heterobimetallic architectures were designed to release and bind guest molecules. The complexes were characterized using various techniques and the disassembly and reassembly process of metallosupramolecular structures were investigated using NMR spectroscopy. Guest binding studies revealed interactions with anionic guests and the release of guests was induced by Cl- ions.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shunlin Zhang, Yuxin Xie, Rosie J. J. Somerville, Farzaneh Fadaei Tirani, Rosario Scopelliti, Zhaofu Fei, Dunru Zhu, Paul J. J. Dyson
Summary: This study reports a new family of proton conductors based on MIL-101 and protic ionic liquid polymers (PILPs) containing different anions. The PILP@MIL-101 composites maintain the nanoporous cavities and water stability of MIL-101, while providing much-improved proton transport. The PILP@MIL-101 composite with HSO4- anions shows superprotonic conductivity (6.3 x 10(-2) S cm(-1)) at 85 degrees C and 98% relative humidity.
Article
Chemistry, Multidisciplinary
Haodan Guo, Yanyan Fang, Yan Lei, Jinpeng Wu, Minghua Li, Xiangrong Li, Hong Bo Cheng, Yuan Lin, Paul J. Dyson
Summary: This study demonstrates the use of a self-assembled ionic insulating layer to improve the performance of wide-bandgap perovskite solar cells. The layer effectively suppresses halide phase separation, reducing open-circuit voltage loss and improving device stability.
Article
Multidisciplinary Sciences
Mingyang Liu, Paul J. Dyson
Summary: Efficient valorization of lignin, a sustainable and renewable source, is essential for reducing dependence on fossil-derived feedstocks. This study presents a highly efficient strategy for extracting aromatic monomers and generating functionalized diaryl ethers from lignin using oxidative cross-coupling reactions.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Alexander Kastner, Hemma Schueffl, Patrick A. Yassemipour, Bernhard K. Keppler, Petra Heffeter, Christian R. Kowol
Summary: Platinum(IV) prodrugs are promising alternatives to platinum(II) anticancer therapeutics. This study investigated the reactivity and synthetic usability of a platinum(IV) complex with hydrolyzable equatorial ligands, and successfully synthesized stable platinum(IV) complexes suitable for long-circulating tumor-targeting strategies. Additionally, platinum(IV) complexes with equatorial maleimides were synthesized, showing prolonged plasma half-life and improved anticancer activity compared to oxaliplatin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Inorganic & Nuclear
Saawan Kumar, Mie Riisom, Stephen M. F. Jamieson, Iman Kavianinia, Paul W. R. Harris, Nils Metzler-Nolte, Margaret A. Brimble, Christian G. Hartinger
Summary: Researchers conjugated a derivative of plecstatin-1 with peptides to enhance their targeting ability towards cancer cells. Metal-peptide conjugates were successfully synthesized and tested for their anticancer activity. Although the activity was relatively low, this study provides a potential strategy to design other metal complexes utilizing the targeting properties of peptides.
INORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Martin Schaier, Enrico Falcone, Tomas Prstek, Bertrand Vileno, Sonja Hager, Bernhard K. Keppler, Petra Heffeter, Gunda Koellensperger, Peter Faller, Christian R. Kowol
Summary: Thiosemicarbazones (TSCs) are biologically active compounds that have potential anticancer activity by chelating iron and targeting ribonucleotide reductase. Recent findings suggest that the stability and reduction properties of copper complexes are essential for the action of specific TSC derivatives. This study investigated the interaction between TSCs and human serum albumin (HSA) as a potential source of copper, and found that TSCs specifically chelate copper from HSA and form ternary HSA conjugates.
Article
Chemistry, Inorganic & Nuclear
Thomas Maier, Judith Wutschitz, Natalie Gajic, Michaela Hejl, Klaudia Cseh, Sebastian Mai, Michael A. Jakupec, Mathea S. Galanski, Bernhard K. Keppler
Summary: This study analyzed the unexpected reaction of (1R,2R)-(cyclohexane-1,2-diamine)dichloridoplatinum(II) with maleic acid and synthesized a series of derivatives with different lipophilicity. The results showed low cytotoxicity and no interaction with DNA for these compounds, indicating their lower reactivity compared to oxaliplatin.
DALTON TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Michael Ramek, Jasmina Sabolovic
Summary: This paper investigates the geometries, energy landscapes, and magnetic parameters of copper(II) amino acid compounds using density functional theory calculations. The results show that certain conformers with histaminate-like and glycine-like modes have low Gibbs free energies and high metal-binding affinities. The predicted conformations reproduce the experimental electron paramagnetic resonance parameters.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Wei Tian, Wen Zhong, Zengyan Yang, Ling Chen, Shijie Lin, Yanping Li, Yuxing Wang, Peilin Yang, Xing Long
Summary: A series of novel dibutyltin complexes based on salen-like ligands were synthesized and characterized. Complex S03 showed excellent in vitro anticancer activity and induced cancer cell death through multiple mechanisms. This study reveals new mechanisms of organotin complexes and provides new insights into the development of organotin metal complexes as anticancer drugs.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Natalie C. Korkola, Martin J. Stillman
Summary: Many proteins require a metal cofactor for their function, and these metals play a role in protein folding. The study found that the metallation rates of different metal binding pathways are influenced by pH, with the less cooperative pathway being more affected by low pH conditions. Specific mixtures of structures are formed in the initial steps of metallation, and unfolding the disordered apo-MT structure hinders the formation of these preliminary structures. The compact conformation of the native apo-MT allows for rapid formation of metal-thiolate structures with high affinity, providing protection from oxidation.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Boxuan Yang, Xitong Song, Binju Wang
Summary: The diiron active site plays a crucial role in catalytic transformations in both biological and chemical systems. Recent advancements in the field include the synthesis of biomimetic diiron catalysts inspired by the active structure of soluble methane monooxygenase (sMMO), which have been successfully applied to the dehydrogenation of indolines.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Christina N. Banti, Angeliki A. Piperoudi, Catherine P. Raptopoulou, Vassilis Psycharis, Constantinos M. Athanassopoulos, Sotiris K. Hadjikakou
Summary: Two copper(I) polymorphs with mitochondria-targeting properties were successfully prepared via metal ion conjugation. These compounds showed promising activities in DNA binding, enzyme inhibition, and cancer cell inhibition. The molecular mechanisms of action were investigated.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)