Article
Chemistry, Inorganic & Nuclear
Ying Tu, Hao-Ming Li, Meng-Meng Wang, Yan Su, Hong-Ke Liu, Zhi Su
Summary: This study developed a dual-targeted platinum (IV) prodrug Pt-CMN, which significantly enhanced anticancer performance and provided a new strategy for enhancing anticancer effects through subcellular organelle targeting.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Anife Ahmedova, Rositsa Mihaylova, Silviya Stoykova, Veronika Mihaylova, Nikola Burdzhiev, Viktoria Elincheva, Georgi Momekov, Denitsa Momekova
Summary: Pt(IV) complexes formed by linking pyrene butyric acid with cisplatin exhibit high anticancer potency against leukemia cells and multidrug-resistant derivatives, while showing low toxicity to healthy cells. The larger bis-pyrene complex is found to potentially be trapped in the cytoskeleton, limiting its cytotoxicity to adherent cells.
Article
Chemistry, Inorganic & Nuclear
Carlo Marotta, Ester Giorgi, Francesca Binacchi, Damiano Cirri, Chiara Gabbiani, Alessandro Pratesi
Summary: The discovery of cisplatin's antineoplastic properties in 1965 renewed the interest in metal complexes for medicinal applications. Researchers have been studying safer and more effective alternatives to cisplatin, including platinum(IV)-based compounds. These compounds have attracted attention because they can be reduced in cells to activate the platinum center and offer advantages such as reducing side effects. This review summarizes the recent achievements in the field of Pt(IV) prodrugs.
INORGANICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Xiyuan Yao, Ulrich Bierbach
Summary: A new assay method using click chemistry-enabled derivative was developed to study DNA damage caused by platinum-acridine anticancer agent in cancer cells. Results showed formation of adducts in specific gene sequences, providing insight into the pharmacological target of these agents.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Analytical
Hao-Xiang Liao, Kazuki Bando, Menglu Li, Katsumasa Fujita
Summary: Cell spheroids provide a complex in vitro cell model similar to in vivo tissues. A multifocal Raman spectrophotometer was developed to enable simultaneous analysis of multiple spheroids, allowing for rapid observation of chemical changes in the spheroids.
ANALYTICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Aleen Khoury, Jennette A. Sakoff, Jayne Gilbert, Kieran F. Scott, Shawan Karan, Christopher P. Gordon, Janice R. Aldrich-Wright
Summary: Platinum(IV) prodrugs showed outstanding activity against various cancer cell lines, with nanomolar activities observed. Cellular accumulation of the complexes was correlated with increased cytotoxicity. COX inhibition or lipophilicity did not solely determine the cytotoxicity of these prodrugs.
Article
Chemistry, Inorganic & Nuclear
Yun-Qiong Gu, Yu-Jun Zhong, Mei-Qi Hu, Huan-Qing Li, Kun Yang, Qi Dong, Hong Liang, Zhen-Feng Chen
Summary: The four copper complexes showed higher cytotoxic activity against various cancer cell lines, especially BEL-7402 cells, with low toxicity to normal human liver cells. Mechanistic studies revealed that they induced apoptosis by inducing G0/G1 arrest and altering the expression of cell cycle-related proteins.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Moyi Liu, Yunli Luo, Junyu Yan, Xiaolin Xiong, Xiwen Xing, Jong Seung Kim, Taotao Zou
Summary: Boronic acid (or ester) is commonly used in the development of anticancer prodrugs, but their application is hindered by low activation efficiency. In this study, a photoactivation approach was developed to convert the boronic acid-caged iridium complex into a bioactive form under hypoxic tumor microenvironments. The mechanism involves the photo-oxidation of phenyl boronate anion to generate a highly reactive phenyl radical, which can capture O2 even at low concentrations. This photoactivation approach shows potent antitumor activities in various experimental models. It can also be extended to activate prodrugs of other anticancer compounds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Inorganic & Nuclear
Zoufeng Xu, Zhigang Wang, Zhiqin Deng, Guangyu Zhu
Summary: Platinum-based anticancer drugs have been widely used in clinical practice for over 40 years, with a focus on developing platinum(IV) prodrugs based on traditional platinum(II) anticancer drugs. Recent progress in the field includes synthesizing platinum(IV) prodrugs with new oxidizing reagents, understanding the hydrolysis and stability of platinum(IV) complexes, and exploring reduction processes to achieve controllable intracellular reduction of platinum(IV) prodrugs. This review aims to enhance researchers' understanding of platinum(IV) anticancer prodrugs and inspire new strategies, ideas, and applications in metal-based drugs.
COORDINATION CHEMISTRY REVIEWS
(2021)
Article
Chemistry, Medicinal
Sheng Cao, Yibin Wang, Daniel Li, Xiaohua Peng
Summary: Researchers synthesized and characterized three compounds with arylboronate esters that selectively react with two equivalents of HN2 to produce DNA cross-linkers. Using HN2 as a leaving group improves the DNA cross-linking efficiency and cytotoxicity against cancer cells. This study provides a strategy for designing potential ROS-activated anticancer prodrugs.
Article
Biochemistry & Molecular Biology
Man Kshetri, Wjdan Jogadi, Suha Alqarni, Payel Datta, May Cheline, Arpit Sharma, Tyler Betters, Deonya Broyles, Yao-Rong Zheng
Summary: We conducted the first comprehensive investigation on the impact of head group modifications on the anticancer activities of fatty-acid-like Pt(IV) prodrugs (FALPs). We created a small library of FALPs with diverse head group modifications and found that hydrophilic modifications enhanced the potency of these metallodrugs, while hydrophobic modifications decreased their cytotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Siming Yuan, Yang Zhu, Yi Dai, Yu Wang, Duo Jin, Manman Liu, Liqin Tang, Fabio Arnesano, Giovanni Natile, Yangzhong Liu
Summary: Pt-IV prodrugs can overcome resistance and side effects of conventional Pt-II anticancer therapies by efficiently promoting the two electrons reduction of Pt-IV to Pt-II. The activation of Pt-FBA is highly dependent upon the type of cancer cells, and FBA can shuttle out of the cell after Pt-FBA is reduced intracellularly. The F-19 NMR approach has the advantage of avoiding the interference of all background signals when investigating the activation of Pt-IV prodrugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Inorganic & Nuclear
Paride Papadia, Alessandra Barbanente, Nicoletta Ditaranto, James D. Hoeschele, Giovanni Natile, Cristina Marzano, Valentina Gandin, Nicola Margiotta
Summary: Six enantiomerically pure, oxaliplatin-like platinum compounds with unsaturated cyclic diamine as a substitute for oxaliplatin were investigated for their promising antiproliferative activities, showing potential in overcoming resistance to platinum-based drugs. The R,R enantiomer was found to be most effective in Pt(ii) complexes while the S,S enantiomer showed greater efficacy in Pt(iv) derivatives, suggesting potential for further preclinical investigation.
DALTON TRANSACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Rebeca Kelly, Diego Aviles, Catriona Krisulevicz, Krystal Hunter, Lauren Krill, David Warshal, Olga Ostrovsky
Summary: High mortality rates in ovarian cancer have been associated with recurrence, metastasis, and chemoresistance, which involve genetic changes and epigenetic aberrations. Adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supporting tumor growth and dissemination through epigenetic abnormalities. Natural epigenetic compounds, such as EGCG and I3C, show promise in reprogramming aberrant epigenetic modifications and suppressing ovarian cancer growth.
Article
Chemistry, Multidisciplinary
Franziska R. Traube, Natercia F. Bras, Wynand P. Roos, Corinna C. Sommermann, Tamara Diehl, Robert J. Mayer, Armin R. Ofial, Markus Mueller, Hendrik Zipse, Thomas Carell
Summary: 5-Aza-2'-deoxycytidine is a drug used to treat myelodysplastic syndrome or acute myeloid leukemia by targeting epigenetic regulation. A recently developed carbocyclic AzadC analogue shows stronger anti-proliferative effects and induces more DNA damage in cancer cells compared to AzadC, making it a promising next generation epigenetic drug.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Inorganic & Nuclear
Alba Hernandez-Garcia, Lenka Markova, Maria Dolores Santana, Jitka Pracharova, Delia Bautista, Hana Kostrhunova, Vojtech Novohradsky, Viktor Brabec, Jose Ruiz, Jana Kasparkova
Summary: This study presents the synthesis and characterization of six new heteroleptic osmium(II) complexes with varying substituents in the R3 position of the phenyl ring of the cyclometalating C^N ligand. These complexes are highly kinetically inert and absorb a full-wavelength range of visible light. The antiproliferative activity of these complexes has been investigated using human cancer and noncancerous cell cultures, showing that they are more potent than conventional cisplatin. The mechanism of action involves the activation of the endoplasmic reticulum stress pathway and disruption of calcium homeostasis.
INORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jaroslav Malina, Hana Kostrhunova, Hualong Song, Peter Scott, Viktor Brabec
Summary: Some metallo-supramolecular helical assemblies that resemble short cationic alpha-helical peptides have been found to target and stabilize DNA G-quadruplexes (G4s) and downregulate G4-regulated genes in human cells. In this study, two pairs of asymmetric Fe(II) triplex metallohelices were investigated for their interaction with five different DNA G4s formed by human telomeric sequence and oncogenes' promoter regions. The metallohelices showed selective binding to G4s over duplex DNA and caused DNA polymerase arrest on G4-containing template strands. Furthermore, the investigated metallohelices suppressed the expression of c-MYC and k-RAS genes at mRNA and protein levels in HCT116 cancer cells.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Hana Kostrhunova, Brondwyn S. McGhie, Lenka Markova, Olga Novakova, Jana Kasparkova, Janice R. Aldrich-Wright, Viktor Brabec
Summary: The platinum(II) complex Pt(II)56MeSS exhibits high potency against cancer cells but also displays side toxicity and in vivo activity. The synthesis of new platinum(IV) prodrugs combining Pt(II)56MeSS with diclofenac (DCF) is described. These Pt(IV) complexes show similar mechanisms of action as Pt(II)56MeSS and DCF, promoting antiproliferative activity and inducing cell death and immunogenic cell death in cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jaroslav Malina, Hana Kostrhunova, Peter Scott, Viktor Brabec
Summary: Fe(II)-based metallohelices were found to stabilize various DNA junctions, with the highest selectivity for the Y-shaped 3WJ. These metallohelices were shown to efficiently kill cancer cells and induce DNA damage, offering potential therapeutic benefits.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Amrita Sarkar, Vojtech Novohradsky, Moumita Maji, Tomer Babu, Lenka Markova, Hana Kostrhunova, Jana Kasparkova, Valentina Gandin, Viktor Brabec, Dan Gibson
Summary: A multitargeting prodrug (2) that releases gemcitabine, oxaliplatin, and doxorubicin in their active form in cancer cells is a potent cytotoxic agent. It selectively targets cancer cells with high selectivity indices and induces the release of DAMPs in CT26 cells. The prodrug also inhibits tumor growth in murine models with lower body weight loss compared to FDA drugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Giulio Bresciani, Jakub Cervinka, Hana Kostrhunova, Lorenzo Biancalana, Marco Bortoluzzi, Guido Pampaloni, Vojtech Novohradsky, Viktor Brabec, Fabio Marchetti, Jana Kasparkova
Summary: This study reports the synthesis of novel diiron complexes with an indole-functionalized vinyliminium ligand and investigates their antiproliferative activity and mechanism of action. The complexes display selective cytostatic effects towards cancer cells, induce apoptosis, and interact with mitochondrial DNA and proteins, as well as exhibit reactive oxygen species (ROS)-scavenging properties and antioxidant activity. This study highlights the importance and therapeutic potential of these diiron complexes as anticancer agents.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Medicinal
Vojtech Novohradsky, Alicia Marco, Lenka Markova, Natalia Cutillas, Jose Ruiz, Viktor Brabec
Summary: In this study, a series of new octahedral iridium(III) complexes Ir1-Ir9 were reported, which showed potential for inhibiting metastasis in triple-negative breast cancer. The results demonstrated that the structural modifications within the complexes strongly influenced their anti-metastatic properties, with complex Ir1 exhibiting the highest activity. Contrary to the effects of the conventional chemotherapy drug doxorubicin, which promoted metastatic properties of TNBC cells, the results suggested that doxorubicin therapy may increase the risk of breast cancer metastasis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jitka Pracharova, Hana Kostrhunova, Alessandra Barbanente, Nicola Margiotta, Viktor Brabec
Summary: RRD2, a phosphaplatin derivative, shows excellent antiproliferative activity in various cancer cell lines by causing DNA lesions and binding to nuclear DNA. It accumulates in cancer cells to a lesser extent than cisplatin but exhibits similar efficiency in binding to nuclear DNA. Activation of RRD2 occurs in the environment of cancer cells, allowing it to bind to nuclear DNA.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
J. P. C. Coverdale, H. Kostrhunova, L. Markova, H. Song, M. Postings, H. E. Bridgewater, V. Brabec, N. J. Rogers, P. Scott
Summary: Self-assembled enantiomers of a di-iron metallohelix showed different antiproliferative activities against HCT116 colon cancer cells, with the ?-helicity compound being more potent than the Delta compound. The accumulation and localization studies suggest that the ? enantiomer undergoes carrier-mediated efflux, while the Delta enantiomer undergoes equilibrative process. The binding of the ? metallohelix to DNA and inhibition of tubulin and actin networks contribute to its G(2)/M arrest effect on cells.
DALTON TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Jitka Pracharova, Hana Kostrhunova, Alessandra Barbanente, Nicola Margiotta, Viktor Brabec
Summary: This study confirms the excellent antiproliferative activity of the phosphaplatin derivative RRD2 in various cancer cell lines and analyzes its binding to nuclear DNA. The results demonstrate that DNA lesions caused by RRD2 contribute to killing cancer cells. Additionally, RRD2 accumulates in cancer cells to a lesser extent than cisplatin but exhibits similar binding efficiency to nuclear DNA after accumulation.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2023)