Article
Chemistry, Inorganic & Nuclear
Zoufeng Xu, Wai Kit Tang, Qiyuan Zhou, Shu Chen, Chi-Kit Siu, Guangyu Zhu
Summary: The study revealed that the hydrolytic stability of Pt(iv) complexes is influenced by other ligands, with successful application to improve the stability of Pt(iv) complexes containing axial dichloroacetate ligands.
INORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Inorganic & Nuclear
Zoufeng Xu, Long Lin, Binbin Fu, Fu-Ping Huang, Qiyuan Zhou, Guangyu Zhu, Zhigang Wang
Summary: The application of new synthetic methods in platinum(iv) anticancer prodrugs increases the availability of accessible entities that can be conjugated to the platinum(iv) center. These new axial ligands not only endow platinum(iv) complexes with unique properties but also inspire new concepts in prodrug design and development.
INORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Qiyuan Zhou, Shu Chen, Zoufeng Xu, Gongyuan Liu, Shuyuan Zhang, Zhigang Wang, Man-Kit Tse, Shek-Man Yiu, Guangyu Zhu
Summary: This study reports the synthesis of Pt-IV complexes bearing axial pyridines through ligand exchange reactions. It was discovered that these axial pyridines can be quickly released after reduction, indicating their potential as axial leaving groups. Two multitargeted Pt-IV prodrugs containing bioactive pyridinyl ligands, a PARP inhibitor and an EGFR tyrosine kinase inhibitor, were successfully obtained using this method. These conjugates show great potential for overcoming drug resistance, with the latter inhibiting the growth of Pt-resistant tumor in vivo. This research expands the synthetic methods for Pt-IV prodrugs and increases the range of bioactive axial ligands that can be conjugated to a Pt-IV center.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Inorganic & Nuclear
Mohammad Taha, Edit Y. Y. Tshuva
Summary: A new series of titanium(iv) complexes based on diaminobis(phenolato)-bis(alkoxo) ligands were synthesized and characterized. The complexes showed enhanced solubility in aqueous media and high hydrolytic stability. They also exhibited cytotoxicity against human cancer cell lines, with the halogenated compounds showing the best combination of stability and activity.
DALTON TRANSACTIONS
(2023)
Review
Biochemistry & Molecular Biology
Daniil Spector, Olga Krasnovskaya, Kirill Pavlov, Alexander Erofeev, Peter Gorelkin, Elena Beloglazkina, Alexander Majouga
Summary: This review summarizes the research on the development of Pt(IV) prodrugs with NSAIDs as axial ligands, their cytotoxic action and anti-inflammatory activity mechanism studies, structure-activity ratio, and therapeutic efficacy. The chemo-anti-inflammatory strategy aims to efficiently deliver cytotoxic metabolites and NSAIDs intracellularly in tumor cells to reduce side effects and increase therapeutic efficacy. Studies have shown high therapeutic efficacy both in vitro and in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Daniil V. Spector, Kirill G. Pavlov, Roman A. Akasov, Alexander N. Vaneev, Alexander S. Erofeev, Petr V. Gorelkin, Vita N. Nikitina, Elena V. Lopatukhina, Alevtina S. Semkina, Kseniya Yu. Vlasova, Dmitrii A. Skvortsov, Vitaly A. Roznyatovsky, Nikolay V. Ul'yanovskiy, Ilya I. Pikovskoi, Sergey A. Sypalov, Anastasiia S. Garanina, Stepan S. Vodopyanov, Maxim A. Abakumov, Yulia L. Volodina, Alina A. Markova, Albina S. Petrova, Dmitrii M. Mazur, Dmitry A. Sakharov, Nikolay V. Zyk, Elena K. Beloglazkina, Alexander G. Majouga, Olga O. Krasnovskaya
Summary: In this study, a series of novel Pt(IV) prodrugs with nonsteroidal anti-inflammatory drugs were designed and synthesized. By tuning the drug lipophilicity via variation of the axial ligands, the most potent Pt(IV) prodrug was obtained, showing enhanced cellular accumulation and cytotoxicity. The prodrugs exhibited superior antiproliferative activity compared to cisplatin and overcame tumor cell line resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Shu Chen, Ka-Yan Ng, Qiyuan Zhou, Houzong Yao, Zhiqin Deng, Man-Kit Tse, Guangyu Zhu
Summary: This study synthesized six mono-carbonated Pt(iv) complexes with axial carbonate ligands of various electron-withdrawing abilities, and prepared corresponding mono-carboxylated analogues as references to investigate the differences in hydrolysis and reduction rates. It was found that mono-carbonated Pt(iv) complexes are less stable and reduced faster compared to mono-carboxylated ones, and the hydrolysis and reduction profiles depend on both the electron-withdrawing ability of the carbonates and the nature of the opposite axial ligands.
DALTON TRANSACTIONS
(2022)
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, Inorganic & Nuclear
Elisabetta Gabano, Marzia Bruna Gariboldi, Giulia Caron, Giuseppe Ermondi, Emanuela Marras, Maura Vallaro, Mauro Ravera
Summary: Octahedral Pt(IV) prodrugs, which combine cisplatin-like moieties and a second drug, are effective in treating glioblastoma. In this study, three Pt(IV) derivatives were synthesized by linking rhein and acetato ligand to a cisplatin core, and they showed higher potency and better blood-brain barrier penetration than the parent drugs. These compounds inhibited tumor progression and reduced cell motility, potentially through the inhibition of MMP2 and MMP9 matrix metalloproteinases.
DALTON TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Ruchika Ojha, Peter C. Junk, Alan M. Bond, Glen B. Deacon
Summary: Pt-IV coordination complexes were synthesized by oxidizing the antitumor agent [Pt-II(p-BrC6F4)NCH2CH2NEt2}Cl(py)]. Experimental data showed that excess H2O2 and elevated temperature favored the oxidation of the ligand, while a smaller amount of H2O2 at room temperature favored the oxidation of the metal, resulting in the formation of platinum(IV) complexes.
Article
Chemistry, Inorganic & Nuclear
Sophia Harringer, Michaela Hejl, Eva A. Enyedy, Michael A. Jakupec, Mathea S. Galanski, Bernhard K. Keppler, Paul J. Dyson, Hristo P. Varbanov
Summary: The study revealed that platinum(iv)-DFO prodrugs exhibit moderate in vitro cytotoxicity with slow activation kinetics across various cancer cell models, showing less pronounced differences between chemoresistant and chemosensitive cell lines as well as between 2D and 3D models compared to clinically used platinum(ii) drug carboplatin.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Inorganic & Nuclear
Juan Carlos Lopez-Lopez, Delia Bautista, Pablo Gonzalez-Herrero
Summary: Unsymmetrical dicarboxylato complexes react with different terminal alkynes to produce various compounds, and these reactions can undergo isomerization, annulation, reduction or coupling processes upon irradiation. The photoreactivity of these complexes is attributed to different excited states, and the products depend on the presence of electron-donating or electron-withdrawing groups on the alkynes. The C-C couplings from certain complexes are attributed to photoreactive pentacoordinate intermediates.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Juan Carlos Lopez-Lopez, Delia Bautista, Pablo Gonzalez-Herrero
Summary: Research shows that unsymmetrical dicarboxylato complexes can react with various terminal alkynes to form different complexes, with the reaction outcome depending on the reaction conditions and light irradiation.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Bin Zhu, Mei Guo, Yi-Chen Yao, Yu-Qian Yao, Minghuang Hong, Ming-Hui Qi, Guo-Bin Ren
Summary: In order to overcome the limitations of oxaliplatin (OXA), such as side effects and toxicity, attention has been given to the use of OXA-based Pt-(IV) complexes as oral prodrugs. This study focused on the preparation and characterization of six cocrystals of trans-[Pt-(R,R-DACH)-(oxalate)-(OH)(2)] (DHOXA) to investigate their stability and reduction rate. The results showed that DHOXA-HYD dihydrate (DHOXA-HYD-DH) significantly improved stability and the reduction rate, and also increased cytotoxicity and safety in cancer cells. This study provides a new method for developing OXA-based Pt-(IV) complexes as prodrugs.
CRYSTAL GROWTH & DESIGN
(2023)
Article
Pharmacology & Pharmacy
Yvonne Lerchbammer-Kreith, Nadine S. Sommerfeld, Klaudia Cseh, Xian Weng-Jiang, Uchechukwu Odunze, Andreas G. Schaetzlein, Ijeoma F. Uchegbu, Mathea S. Galanski, Michael A. Jakupec, Bernhard K. Keppler
Summary: A new class of anticancer prodrugs was developed by combining platinum(IV) complexes with glycol chitosan polymers as drug carriers. The platinum(IV) complexes were synthesized and conjugated with degraded glycol chitosan (dGC) polymers of different chain lengths. These conjugates exhibited higher cytotoxicity and antiproliferative activity in cancer cell lines compared to platinum(IV) counterparts. In particular, a cisplatin(IV)-dGC conjugate showed the highest cytotoxicity, being 33 times more potent than the corresponding platinum(IV) complex and twice as potent as cisplatin. Biodistribution studies of an oxaliplatin(IV)-dGC conjugate also showed increased accumulation in the lung, suggesting potential for further activity studies.
Article
Chemistry, Inorganic & Nuclear
Shuang Li, Jian Zhao, Xinyi Wang, Gang Xu, Shaohua Gou, Qiang Zhao
INORGANIC CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Jian Zhao, Kaiwen Yan, Gang Xu, Xue Liu, Qiang Zhao, Chenjie Xu, Shaohua Gou
Summary: Iridium(III) complexes with donor-acceptor-donor structure exhibit high ROS generation efficiency and photothermal therapy effect under NIR stimulation. The self-assembled metallosupramolecular aggregates of the complex show unique aggregation-induced PDT behavior and significant tumor inhibition in cancer phototherapy, with tumor volume reduction of 96% and even tumor elimination.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Chemistry, Inorganic & Nuclear
Tianyu Han, Yuying Wu, Weinan Han, Kaiwen Yan, Jian Zhao, Yanyan Sun
Summary: The facile modification of ligands in organometallic Ru(II)-arene complexes provides more opportunities for optimizing their pharmacological profiles. This study designed and synthesized three Ru(II)-arene complexes containing a GST inhibitor (NBDHEX), with in vitro results showing increased activities against tumor cells, especially in complex 3 which demonstrated the highest activity. Complex 3, with more alkyl groups in the arene ligand, exhibited increased electron density at the Ru(II) center leading to improved hydrolysis rate and higher anticancer activity.
INORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Gang Xu, Chengwei Li, Chen Chi, Luyan Wu, Yanyan Sun, Jian Zhao, Xing-Hua Xia, Shaohua Gou
Summary: The researchers reported a near-infrared supramolecular photosensitizer, RuDA, which can produce singlet oxygen in aggregate state and induce tumor regression in vivo.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Inorganic & Nuclear
Zichen Xu, Yongzhi Yu, Jian Zhao, Zhixin Liao, Yanyan Sun, Si Cheng, Shaohua Gou
Summary: Tumor hypoxia severely affects the efficiency of photodynamic therapy. This study presents a chemo-photodynamic antitumor strategy using ultrathin graphitic carbon nitride nanosheets loaded with a hypoxia-targeting platinum(IV) prodrug. Under low-intensity visible light irradiation, this strategy effectively generates reactive oxygen species and inhibits tumor proliferation.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Yuliang Yang, Xiaofeng Zou, Yanyan Sun, Feihong Chen, Jian Zhao, Shaohua Gou
Summary: This article presents a rational design of half-sandwich Ru(II) complexes for mitochondria-targeted anticancer and antimetastatic agents by introducing the NDI unit into the N,N-chelating ligand of these complexes, which exhibit excellent emission performance. These complexes have potential applications in the design of multifunctional theranostic agents and fluorescent biomarkers.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jian Zhao, Ya Gao, Rong Huang, Chen Chi, Yanyan Sun, Gang Xu, Xing-Hua Xia, Shaohua Gou
Summary: The intermolecular coupling of well-designed photosensitizers has the potential to inhibit vibrational relaxation and enhance phototherapeutic efficacy. Experimental validation showed that the synthesized metallo-photosensitizers exhibited enhanced singlet oxygen generation efficiency and high biocompatibility.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Materials Science, Multidisciplinary
Jian Zhao, Rong Huang, Ya Gao, Jiadong Xu, Yanyan Sun, Jiayuan Bao, Lei Fang, Shaohua Gou
Summary: The development of near-infrared (NIR) Type-I photosensitizers is drawing great attention to overcome the limitations of traditional O-2-dependent Type-II photosensitizers. A promising concept is proposed to lower the energy of the lowest triplet excited state (T-1) of the photosensitizer below the threshold for oxygen sensitization by maximizing the electronic exchange energy. By utilizing the low-energy intramolecular charge transfer (ICT) state, pyrrolidine is conjugated with perylenediimide (PDI) to produce a novel photosensitizer, PDIPy, with NIR absorbance and low T-1 energy level. Supramolecular nanoparticles (NanoPDIPy) assembled from PDIPy demonstrate excellent phototherapeutic efficacy against cancer in vitro and in vivo under either normoxia or hypoxia upon 730 nm laser irradiation.
ACS MATERIALS LETTERS
(2023)
Article
Chemistry, Medicinal
Yuliang Yang, Ya Gao, Yanyan Sun, Jian Zhao, Shaohua Gou
Summary: A series of novel ruthenium(II) and iridium(III) complexes with different ancillary ligands and a PARP-1-inhibitory chelating ligand were designed and synthesized. The complexes exhibited potent antiproliferative activity on cancer cell lines, with the ruthenium(II) complexes being more cytotoxic. The most active ruthenium complex induced apoptosis in cancer cells through multiple mechanisms.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Mengzhu Wang, Nan He, Runze Tang, Feiyang Li, Shujuan Liu, Feng Xu, Jian Zhao, Yi Tong, Qiang Zhao
Summary: A novel Ru(II) complex with a donor-acceptor-donor (D-A-D) ligand was synthesized for organic memory devices, which exhibited obvious bipolar resistance switching behavior with a low switching voltage (approximately 1.13 V) and a large ON/OFF ratio (10^5). The dominant switching mechanism was attributed to distinct charge-transfer states caused by the interaction between metals and ligands, as confirmed by density functional theory (DFT) calculations. This work not only unveils the potential of the Ru(II) complex in resistive switching devices, but also provides new inspiration for manipulating the switching voltage at the molecular level.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Multidisciplinary
Lei Fang, Rong Huang, Wenqi Gong, Yuanhui Ji, Yanyan Sun, Shaohua Gou, Jian Zhao
Summary: This study proposes an effective approach to improve the electron transfer efficiency of Type-I photosensitizers by self-assembly-induced exciton delocalization. A proof of concept is demonstrated using a perylene diimide-based photosensitizer that can generate singlet oxygen in the monomeric state, but superoxide anion in the aggregated state. The addition of a specific substance can revert the aggregated state back to monomeric state, resulting in the recovery of singlet oxygen generation. The supramolecular nanoparticles derived from this photosensitizer show superior phototherapeutic performance against cancer through synergistic Type-I PDT and mild PTT.
Article
Materials Science, Multidisciplinary
Chengwei Li, Ya Gao, Rong Huang, Lei Fang, Yanyan Sun, Yuliang Yang, Shaohua Gou, Jian Zhao
Summary: Researchers have successfully designed and synthesized a novel PDI-based photosensitizer with excellent water dispersity and intense near-infrared absorbance, which can efficiently generate singlet oxygen. This study has the potential to expand the application of near-infrared-absorbing photosensitizers and provide a solution to overcome limitations in clinical use.
ACS MATERIALS LETTERS
(2022)
Article
Chemistry, Inorganic & Nuclear
Weinan Han, Weiyu He, Yutong Song, Jian Zhao, Zhiheng Song, Yi Shan, Wuyang Hua, Yanyan Sun
Summary: A multifunctional platinum(IV) compound with tumor-targeting ability and simultaneous targeting of DNA and histone deacetylase (HDAC) has been designed and prepared. In vitro experiments showed that the compound exhibited higher cytotoxicity against cancer cell lines and lower toxicity against normal cells compared to cisplatin.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Bin Zhang, Zichen Xu, Wen Zhou, Zhikun Liu, Jian Zhao, Shaohua Gou
Summary: A hypoxia-activated bifunctional prodrug was designed and encapsulated by a photo-responsive polymer to create a light-controlled multi-step drug release system for tumor hypoxia therapy. In vivo studies demonstrated that the prodrug exhibited high efficiency in tumor regression through the synergistic effect of photodynamic therapy and hypoxia-activated chemotherapy.
Article
Chemistry, Inorganic & Nuclear
Shuang Li, Gang Xu, Yuhua Zhu, Jian Zhao, Shaohua Gou
DALTON TRANSACTIONS
(2020)