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
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
Jiafan Lin, Jishuai Zhang, Ziqi Ma, Xiaoqin Wu, Fuyi Wang, Yao Zhao, Kui Wu, Yi Liu
Summary: The interaction between a photoactivatable Pt(iv) prodrug and human telomeric DNA was studied. Two major mono-platinated DNA adducts were detected, with trans-[Pt-II(N-3)(py)(2)](+) and trans-[Pt-II(py)(2)](2+) as the bound Pt moieties. The platination sites were found to be G(6) and A(3) in one adduct, and a potential intrastrand crosslink was speculated after G(4) and G(6) in the other adduct. Minor platinated adducts and oxidized DNA adducts were also observed. These results provide valuable chemical information about the photoreaction between photoactivatable Pt(iv) anticancer prodrugs and human telomeric DNA.
DALTON TRANSACTIONS
(2023)
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)
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, Inorganic & Nuclear
Ran Zhang, Yueyue Zhang, Liumei Tang, Yixing Xu, Hao Li, Xueping Jiang, Xiangdong Xin, Zhongzheng Gui
Summary: A series of Pt(IV) prodrugs containing a microtubule inhibitor paclitaxel were synthesized and evaluated for their antitumor activity. One of the prodrugs, named Ptxplatin, effectively entered cancer cells and induced DNA damage, cell cycle arrest, and inhibition of cell migration. Furthermore, Ptxplatin caused mitochondrial dysfunction and triggered endoplasmic reticulum stress, ultimately leading to cancer cell death.
INORGANIC CHEMISTRY FRONTIERS
(2022)
Review
Chemistry, Multidisciplinary
Johannes Karges
Summary: Platinum(II) complexes are widely used in chemotherapy, but are associated with severe side effects and poor tumor selectivity. To address this issue, platinum(IV) molecular prodrugs and nanoparticle formulations that can be activated into therapeutically active analogs through specific triggers have been explored. This article critically reviews the mechanisms for activating platinum(IV) prodrugs using chemical and photophysical triggers.
Article
Chemistry, Multidisciplinary
Alessandra Barbanente, Valentina Gandin, Chiara Donati, Carmela Ilaria Pierro, Giovanni Natile, Nicola Margiotta
Summary: Platinum-based drugs have been successful in treating solid tumors, but toxicity and resistance limit their outcomes. Natural products, such as 10-HDA found in royal jelly, are being explored as safe and easily available anti-cancer drugs. In this study, the researchers aimed to combine the functionality of 10-HDA with platinum to develop new compounds with potential anti-cancer activity. The synthesized compounds were characterized and tested for their cytotoxicity against human tumor cell lines. The results showed that some of the new compounds exhibited promising activity against specific tumor cell lines.
NEW JOURNAL OF CHEMISTRY
(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
Biophysics
Ping-Hsuan Wu, Pei-Fen Cheng, Watchareeya Kaveevivitchai, Teng-Hao Chen
Summary: Manipulating Fenton chemistry in tumor microenvironment (TME) for the generation of reactive oxygen species is an effective strategy for chemodynamic therapy. Here, a nanozyme MOF-Pt(IV)@GOx was developed by covalently grafting a prodrug of cisplatin (Pt(IV) prodrug) onto a ferric metal-organic framework (MOF) and loading it with a biocatalyst glucose oxidase (GOx). The system achieved synergistic trimodal therapy consisting of ferroptosis, starvation therapy, and chemotherapy, by enhancing GOx loading and chemotherapy, reducing Fe(III) to Fe(II) for Fenton reaction, converting Pt(IV) prodrug to cisplatin, and promoting intracellular acidity and H2O2 supply in TME.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Chemistry, Multidisciplinary
M. K. Pal, A. G. Majumdar, K. V. Vivekananda, A. P. Wadawale, M. Subramanian, N. Bhuvanesh, S. Dey
Summary: A series of Pt metallacycles were constructed and their structures and stability were studied. The new Pt complexes showed low antiproliferative activity but high induction of apoptosis and DNA damage.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Engineering, Biomedical
Maria Sancho-Albero, Giorgio Facchetti, Nicolo Panini, Marina Meroni, Ezia Bello, Isabella Rimoldi, Massimo Zucchetti, Roberta Frapolli, Luisa De Cola
Summary: Platinum-based chemotherapy is the standard first-line treatment for various types of cancer, including malignant pleural mesothelioma. This study presents a strategy using a breakable nanocarrier to stabilize, transport, and release a platinum(IV) prodrug, which is activated by the presence of glutathione in neoplastic cells. In vitro and in vivo experiments demonstrate the successful release and activation of the Pt-based drug inside cancer cells, leading to a significant reduction in tumor growth.
ADVANCED HEALTHCARE MATERIALS
(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, Physical
Fortuna Ponte, Stefano Scoditti, Gloria Mazzone, Emilia Sicilia
Summary: Octahedral Pt-IV complexes show promise as alternatives to Pt-II drugs, as they have the ability to resist premature hydrolysis and unwanted binding in plasma. These compounds can be orally administered and have the potential to reduce side effects. The activation mechanism of Pt-IV prodrugs remains poorly understood, but computational studies are providing insights into this process.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Review
Biochemistry & Molecular Biology
Daniil Spector, Kirill Pavlov, Elena Beloglazkina, Olga Krasnovskaya
Summary: Pt(IV) prodrugs with a light-controlled mode of activation show high antiproliferative activity when irradiated, but are non-toxic in the absence of light. This review discusses recent advances in photoabsorber-mediated photocontrollable activation of Pt(IV) prodrugs, focusing on the photocatalytic strategy based on flavin derivatives and the conjugation of photoactive molecules with Pt(II) drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Inorganic & Nuclear
Yanpeng Liu, Houzong Yao, Man-Kit Tse, Shu Chen, Shek-Man Yiu, Guangyu Zhu
Summary: By designing and synthesizing a Pt(IV) monotrifluoromethyl complex, we have increased its reactivity and discovered its ability to react with phosphates via the S(N)2 nucleophilic substitution pathway, which is different from traditional Pt(II) drugs. This complex exhibits cytotoxicity in human ovarian cancer cells and may serve as a potential new anticancer agent.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Chen Cao, Ji-Hua Tan, Ze-Lin Zhu, Jiu-Dong Lin, Hong-Ji Tan, Huan Chen, Yi Yuan, Man-Kit Tse, Wen-Cheng Chen, Chun-Sing Lee
Summary: By intramolecular cyclization in a carbonyl/N resonant core (QAO), a deep-blue emitter (CZ2CO) with a peak wavelength of 440 nm and an ultranarrow spectral FWHM of 16 nm (0.10 eV) was developed. CZ2CO exhibits excellent performance that complies with the BT.2020 standard. Additionally, a hyper-fluorescent device based on CZ2CO achieves a high maximum external quantum efficiency (EQE(max)) of 25.6% and maintains an EQE of 22.4% at a practical brightness of 1000 cd m(-2).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Libei Huang, Le Cheng, Tinghao Ma, Jun-Jie Zhang, Haikun Wu, Jianjun Su, Yun Song, He Zhu, Qi Liu, Minghui Zhu, Zhiyuan Zeng, Qiyuan He, Man-Kit Tse, Deng-tao Yang, Boris I. Yakobson, Ben Zhong Tang, Yang Ren, Ruquan Ye
Summary: Amorphous graphene synthesized by laser induction is shown to efficiently electrocatalyze the reduction of nitrate to ammonia, with high conversion efficiency and production rate. This method has significant potential for the on-demand synthesis of ammonia in agriculture and pharmaceutical industries, resulting in increased yields and survival rates for plant cultivation.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Jia Tang, Yudai Matsuda
Summary: In this study, the researchers investigated the catalytic functions of Pyr4-family terpene cyclases by conducting mutational experiments on AdrI and its homologues. They discovered that AdrI and InsA7, which accept the same substrate, use different amino acid residues to initiate the cyclization cascade. Additionally, they obtained variants of AdrI with altered product selectivity, leading to the discovery of a new meroterpenoid species. This research provides valuable insights into the catalytic mechanisms of Pyr4-family terpene cyclases and has implications for enzyme engineering.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(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
Biochemistry & Molecular Biology
Qingting Zeng, Hao Cui, Houzong Yao, Tao Yuan
Summary: Five eremophilane sesquiterpenes, including three new compounds named paraconions A-C (1-3), were isolated from an endophytic fungus, Paraconiothyrium sp., found in Artemisia selengensis. The structures of these new compounds were identified through spectroscopic methods including NMR, UV, IR, and HR-ESI-MS. One of the compounds, paraconion B (2), demonstrated anti-inflammatory activity by inhibiting lipopolysaccharide-induced NO production in RAW 264.7 cells with an IC50 value of 51.7 μM. The discovery of these compounds enriches the diversity of secondary metabolites produced by the endophytic fungus Paraconiothyrium sp.
CHEMISTRY & BIODIVERSITY
(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
Chemistry, Multidisciplinary
Zhiqin Deng, Huangcan Li, Shu Chen, Na Wang, Gongyuan Liu, Danjun Liu, Weihui Ou, Feijie Xu, Xiong Wang, Dangyuan Lei, Pui-Chi Lo, Yang Yang Li, Jian Lu, Mengsu Yang, Ming-Liang He, Guangyu Zhu
Summary: This study reports the use of near-infrared-activated small-molecule Pt(IV) photooxidants to directly oxidize intracellular biomolecules. These photooxidants can effectively eliminate cancer stem cells and show low toxicity in the dark. Metal-enhanced photooxidation induced by these Pt(IV) complexes leads to robust photooxidation of survival-related biomolecules, inducing oxidative stress, disrupting intracellular pH (pHi) homeostasis, and initiating nonclassical necrosis.
Article
Multidisciplinary Sciences
Gongyuan Liu, Yachao Zhang, Houzong Yao, Zhiqin Deng, Shu Chen, Yue Wang, Wang Peng, Guohan Sun, Man-Kit Tse, Xianfeng Chen, Jianbo Yue, Yung-Kang Peng, Lidai Wang, Guangyu Zhu
Summary: In this work, cyaninplatin, a Pt(IV) anticancer prodrug, is introduced, which can be activated by ultrasound. The sono-activation of cyaninplatin leads to strengthened mitochondrial DNA damage and cell killing efficiency, along with overcoming drug resistance. This study demonstrates the practical utility of ultrasound in activating Pt(IV) anticancer prodrugs for the eradication of deep tumor lesions.
Article
Chemistry, Physical
Yelan Xiao, Yecheng Leng, Xinxin Lu, Shun-Cheung Cheng, Hao Huang, Man-Kit Tse, Jiechun Liang, Wenguang Tu, Chi-Chiu Ko, Xi Zhu, Lu Wang, Yong Zhou, Yingfang Yao, Zhigang Zou
Summary: Photocatalytic radical fluoroalkylation is an important method to prepare organofluorine compounds. This study introduces a cost-effective and recyclable heterogeneous photocatalysis using cyano-modified graphitic carbon nitride as the photocatalyst. The photocatalytic process is attributed to the long-lived triplet excited states and the strong interaction between the catalyst and substrate. Moreover, the catalyst shows high performance, wide reaction scope, and can be easily recovered and reused for multiple catalytic cycles.
JOURNAL OF CATALYSIS
(2023)
Review
Biochemistry & Molecular Biology
Zhiqin Deng, Shu Chen, Gongyuan Liu, Guangyu Zhu
Summary: This review provides a summary of strategies that target specific organelles in cancer cells, promoting increased anticancer activity, overcoming drug resistance, altering the action mode, and reducing toxicity of platinum complexes.
RSC CHEMICAL BIOLOGY
(2023)
