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
Biochemistry & Molecular Biology
Marie-Christin Barth, Norman Haefner, Ingo B. B. Runnebaum, Wolfgang Weigand
Summary: The research explores the anticancer potential of platinum(IV) complexes and investigates the effects of non-steroidal anti-inflammatory drug (NSAID) ligands on their cytotoxicity. The synthesis and characterization of nine platinum(IV) complexes are presented, and their cytotoxic activity is evaluated against ovarian carcinoma cell lines. The most promising complex, Compound 7, induces cell cycle arrest and apoptosis or necrosis in a cell line-dependent manner, acting through a stress response pathway involving p21, CHOP, and ATF3 genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Angelico D. Aputen, Maria George Elias, Jayne Gilbert, Jennette A. Sakoff, Christopher P. Gordon, Kieran F. Scott, Janice R. Aldrich-Wright
Summary: The DNA-alkylating derivative chlorambucil was coordinated with atypical cytotoxic platinum(IV) complexes, resulting in prodrugs with remarkable antitumor potential. The prodrug 56CLB showed exceptionally high activity in multiple cancer cell lines and induced significant production of reactive oxygen species in treated cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Jun Xiang Ong, Hai Van Le, Violet Eng Yee Lee, Wee Han Ang
Summary: Mitochondria have been identified as important targets for cisplatin in cancer treatment. In addition to cisplatin, anticancer Pt complexes with similar structures have been developed to target mitochondria. The researchers developed a mitochondria-targeted fluorescent probe to monitor Pt accumulation in mitochondria in real time, and identified two distinct pathways through which Pt complexes could be delivered to mitochondria.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Rui Li, Weiheng Zhao, Chen Jin, Huihua Xiong
Summary: Researchers synthesized and evaluated nine novel platinum(IV) complexes modified with Olaparib's key pharmacophore for their biological activities. The optimal complex 8-2 showed good inhibitory activity against PARP-1 and superior anticancer effects over CDDP. Mechanistically, 8-2 efficiently reversed CDDP resistance by increasing its intracellular accumulation and activating DNA damage and apoptosis pathways. Furthermore, 8-2 exhibited higher tumor growth inhibition rate than CDDP without inducing significant toxicity, making it a potential drug candidate for TNBC treatment.
BIOORGANIC CHEMISTRY
(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
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
Materials Science, Biomaterials
Tushar Date, Kaushik Kuche, Dasharath Chaudhari, Rohan Ghadi, Deepak Kumar Sahel, Deepak Chitkara, Sanyog Jain
Summary: The developed cisplatin(IV) derivatives exhibit enhanced antiproliferative activity and improved therapeutic synergism in triple-negative breast cancer, leading to a reduction in cisplatin dosage and mitigating nephrotoxicity risks. These derivatives also demonstrate increased cellular drug uptake and decreased dependency on copper transporter 1 compared to cisplatin.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2022)
Article
Chemistry, Multidisciplinary
Nafees Muhammad, Tan Cai-Ping, Sadia Nasreen, Zong-Wan Mao
Summary: A mitochondria targeting dual-action platinum(IV) prodrug shows high anticancer activity in triple negative breast cancer cells by intervening in various cellular processes, ultimately killing cancer cells through DNA damage, perturbation of mitochondrial bioenergetics, and induction of necrosis.
CHEMISTRY-AN ASIAN JOURNAL
(2021)
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
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
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, Medicinal
Qinghe Yang, Gang Li, Weifeng Li, Tian Cai, Hang Liu, Yiming Zhao, Yabing Zhang, Hengshan Wang
Summary: This study synthesized six novel ligustrazine-derived chalcones-modified platinum(IV) complexes and found that one of the compounds, 16a, exhibited better anti-cancer activity and lower toxicity to normal cells compared to CDDP. Mechanistic studies showed that 16a induced DNA damage and initiated a mitochondria-dependent apoptosis pathway, and it also triggered ferroptosis significantly.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Javier E. Lopez-Hernandez, Nazia Nayeem, Jose P. Ceron-Carrasco, Afruja Ahad, Aiman Hafeez, Ignacio E. Leon, Maria Contel
Summary: This study describes new heterometallic binuclear and trinuclear platinum(IV)-gold(I) compounds that exhibit cytotoxicity and selectivity against a small panel of cancer cell lines. One trinuclear compound accumulates in the nucleus and mitochondria, induces apoptosis, and shows antimigratory and antiangiogenic properties against triple-negative breast cancer (TNBC) cell lines, as well as potent cytotoxic effect against TNBC 3D spheroids.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Xue-Qing Song, Rui-Ping Liu, Shu-Qing Wang, Zhe Li, Zhong-Ying Ma, Ran Zhang, Cheng-Zhi Xie, Xin Qiao, Jing-Yuan Xu
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Applied
Ling-Wen Xu, Xin-Tian Wang, Yun-Hong Zou, Xu-Ya Yu, Cheng-Zhi Xie, Xin Qiao, Qing-Zhong Li, Jing-Yuan Xu
APPLIED ORGANOMETALLIC CHEMISTRY
(2020)
Article
Pharmacology & Pharmacy
Zhong-Ying Ma, Xue-Qing Song, Juan-Juan Hu, Dong-Bo Wang, Xiao-Jing Ding, Rui-Ping Liu, Miao-Liang Dai, Fan-Yin Meng, Jing-Yuan Xu
Summary: Ketoplatin, a platinum(IV) conjugate derived from cisplatin and ketoprofen, exhibits strong inhibitory effects on triple-negative breast cancer by suppressing EMT progression through COX-2 modulation, reducing cellular DNA damage, and showing high anti-tumor activity and low toxicity in vitro and in vivo.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Xin Qiao, Yu-Yang Gao, Li-Xia Zheng, Xiao-Jing Ding, Ling-Wen Xu, Juan-Juan Hu, Wei-Zhen Gao, Jing-Yuan Xu
Summary: Lipid metabolism alterations are recognized as a hallmark for cancer, and modifying cisplatin with the hypolipidemic drug bezafibrate has resulted in enhanced anticancer activity with lower toxicity to normal cells. The novel platinum-based agents show mechanistically distinct antitumor action compared to conventional platinum drugs, indicating a potential novel strategy for cancer treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Spectroscopy
Xiao-Jing Yan, Yu-Yang Gao, Hai-Bo Liu, Xin Qiao, Cheng-Zhi Xie, Qing-Zhong Li, Wei-Zhen Gao, Hua-Bing Sun, Jing-Yuan Xu
Summary: A novel fluorescence probe NHMI was developed for fast and selective detection of Al3+ and Mg2+, showing potential application in biological diagnostic analysis at the cellular level.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Pharmacology & Pharmacy
Chun-Lai Zhao, Xin Qiao, Xiao-Meng Liu, Xue-Qing Song, Dan-Qing Li, Xia-Wen Yu, Wei-Guo Bao, Jing-Yuan Xu
Summary: This study demonstrates that Pt(IV) complex oxoplatin can bind to DNA in a tetravalent state and rapidly produce stable interstrand crosslinks, leading to cancer cell death. Additionally, oxoplatin can induce a quick intracellular response of the FA/BRCA pathway in cancer cells, independent of intracellular glutathione levels.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Xiao-Meng Liu, Zhe Li, Xin-Ru Xie, Jia-Qian Wang, Xin Qiao, Cheng-Zhi Xie, Jing-Yuan Xu
Summary: Exploring multi-targeting chemotherapeutants with advantages over single-targeting agents and drug combinations is of great significance in Drug discovery. By functionalizing platinum drugs with multi-target EVO, compound 10 demonstrated superior anticancer activity with low toxicity and decreased resistance, representing a new cancer therapy modality.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Zhe Li, Xin Qiao, Xiao-Meng Liu, Shu-Hao Shi, Jing-Yuan Xu
Summary: In this study, riluzole-Pt(IV) compounds were synthesized to target multiple pathways and achieve a synergistic anticancer effect. Compound 2 showed excellent antiproliferative activity and selectivity compared to cisplatin. Mechanism studies revealed that compound 2 released riluzole and active Pt(II) species, leading to DNA damage, cell apoptosis, and inhibition of metastasis. It also blocked glutathione biosynthesis and targeted hERG1, suppressing cancer cell growth and reversing EMT. These riluzole-Pt(IV) prodrugs are promising candidates for cancer treatment compared to traditional platinum drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Zhen-Lei Zhang, Rui Rong, Xuan-Lin Ren, Ling-Wen Xu, Wen-Jing Lian, Xin Qiao, Jing-Yuan Xu
Summary: Unrestricted cell growth and proliferation of cancer cells correlate with accelerated RNA polymerase I transcription and upregulation of ribosome biogenesis. CX-5461, a Pol I selective inhibitor with multitargeting property and synthetic lethality in HR-deficient cancers, was used to modify cisplatin to obtain two monofunctional platinum Pol I selective inhibitors. The study demonstrated that P1-Q1 and P1-Q2 could specifically target Pol I transcription machinery and overcome platinum drug resistance in BRCA1-deficient A549 cells.
INORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Inorganic & Nuclear
Xiao-Meng Liu, Zhe Li, Xin-Rui He, Rui-Ping Liu, Zhong-Ying Ma, Xin Qiao, Shu-Qing Wang, Jing-Yuan Xu
Summary: The study designed and prepared a new class of multi-targeting Pt(IV) prodrugs using the FDA-approved aromatase inhibitor aminoglutethimide, with a representative compound aminoplatin 3 showing enhanced anticancer activity and lower toxicity compared to cisplatin in ER-positive MCF-7 cells.
INORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Juan-Juan Hu, Zhong-Ying Ma, Xin-Rui He, Yi-Gang Wu, Qian Chen, Xue-Qing Song, Guan-Yuan Wang, Yi-Han Li, Jing-Yuan Xu
Summary: Gastric adenocarcinomas with elevated COX-2 expression can be inhibited by Pt(IV) complexes synthesized with non-steroidal anti-inflammatory drugs as ligands, leading to suppressed growth and metastasis of gastric cancer cells.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Materials Science, Biomaterials
Zhi-Gang Wang, Xiao-Jing Yan, Hai-Bo Liu, De-Long Zhang, Wei Liu, Cheng-Zhi Xie, Qing-Zhong Li, Jing-Yuan Xu
JOURNAL OF MATERIALS CHEMISTRY B
(2020)
Article
Chemistry, Inorganic & Nuclear
Xiao-Jing Ding, Ran Zhang, Rui-Ping Liu, Xue-Qing Song, Xin Qiao, Cheng-Zhi Xie, Xiu-He Zhao, Jing-Yuan Xu
INORGANIC CHEMISTRY FRONTIERS
(2020)
Article
Chemistry, Inorganic & Nuclear
Ming Liu, Xue-Qing Song, Yuan-Di Wu, Jing Qian, Jing-Yuan Xu
DALTON TRANSACTIONS
(2020)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)