Article
Biochemistry & Molecular Biology
Fu-Li Xie, Zhi-Tong Huang, Lan Bai, Jian-Wei Zhu, Hui-Hua Xu, Qing-Qin Long, Qi-Feng Guo, Yong Wu, Si-Hong Liu
Summary: Two iridium (III) polypyridine complexes were synthesized and encapsulated in liposomes, showing high cytotoxicity against cancer cells while having no significant toxicity towards non-cancer cells. The complexes inhibit cell proliferation, induce cell cycle arrest, and affect mitochondrial function and ROS levels, suggesting a potential mechanism of action through ROS-mediated mitochondrial dysfunction and activation of PI3K/AKT signaling pathways in cancer cells.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Zhen-Feng Wang, Xiao-Ling Nai, Yue Xu, Feng-Hua Pan, Fu-Shun Tang, Qi-Pin Qin, Lin Yang, Shu-Hua Zhang
Summary: Four novel rhodium(iii) complexes were synthesized and found to exhibit selective cytotoxicity against cisplatin-resistant lung carcinoma cells. One of the complexes, a fluorescent imaging agent, showed high anticancer activity in the cell nucleus.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Jong Hyun Kim, Samuel Ofori, Sean Parkin, Hemendra Vekaria, Patrick G. Sullivan, Samuel G. Awuah
Summary: Expanding the chemical diversity of metal complexes by creating organometallic gold(III) compounds provides a powerful platform for generating functional bioactive reagents. The lead compound AuPhos-89 demonstrates potent anti-cancer activity by modulating mitochondrial respiration to inhibit tumor growth of metastatic triple negative breast cancer.
Article
Biochemistry & Molecular Biology
Yan-Bo Peng, Can Tao, Cai-Ping Tan, Ping Zhao
Summary: Rhodium complexes have been recently studied for their tunable properties with attractive anticancer activity. The synthesized complexes Rh1 and Rh2 show stronger anticancer activity than cisplatin against various cancer cells, targeting mitochondria through inducing apoptosis, regulating gene expression, and elevating reactive oxygen species levels. This work provides a strategy for constructing highly effective anticancer agents through rational modification of rhodium complexes targeting mitochondrial metabolism.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Leide Laura Figueiredo Maciel, Marina Barreto Silva, Rafaela Oliveira Moreira, Ana Paula Cardoso, Christiane Fernandes, Adolfo Horn Jr, Joao Carlos de Aquino Almeida, Milton Masahiko Kanashiro
Summary: This study investigated the antineoplastic activity of two platinum complexes containing alpha- and beta-naphthyl groups. The results showed that one of the platinum complexes exhibited higher cytotoxicity against all cancer cell lines tested and lower cytotoxicity against normal peripheral blood mononuclear cells. Further investigations revealed that this complex induced cell death by apoptosis and was associated with mitochondrial membrane depolarization, elevated levels of reactive oxygen species (ROS), and caspase activation.
Article
Biochemistry & Molecular Biology
Wenlong Li, Xiaoyu Wu, Haimei Liu, Chuanling Shi, Yuhan Yuan, Lan Bai, Xiaofei Liao, Yuanyuan Zhang, Yunjun Liu
Summary: In this study, two new iridium(III) complexes were synthesized and their anticancer activity was evaluated. The complexes showed no or low cytotoxic activity against the selected cancer cells. However, when encapsulated into liposomes, the complexes exhibited higher anticancer efficacy and induced apoptosis through different pathways.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Chemistry, Applied
Snezana Radisavljevic, Ana Kesic, Dusan Cocic, Vladimir Markovic, Jelena Milovanovic, Biljana Petrovic, Ana Rilak Simovic
Summary: In this work, a new monofunctional gold(III) complex was synthesized and characterized. The substitution reactions between the complex and biomolecules were found to be dependent on the nature of the entering nucleophile. The substitution mechanism was proposed to be associative based on the calculated values of entropy and enthalpy. Additionally, the complex interacted with DNA and protein, exhibited significant cytotoxic activity against human oral squamous carcinoma cells, and affected cell cycle and proliferation.
APPLIED ORGANOMETALLIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Valerio Giuso, Jeannine Yang, Jeremy Forte, Heloise Dossmann, Chantal Daniel, Christophe Gourlaouen, Matteo Mauro, Benoit Bertrand
Summary: A series of binuclear gold complexes have been synthesized and characterized. These complexes exhibit long-lived yellow-green phosphorescence in the solid state with high photoluminescence quantum yields. Two of the complexes show promising antiproliferative activity against lung adenocarcinoma cells.
Article
Environmental Sciences
Weiqi Sun, Zhijing Ni, Rui Li, Xiuli Chang, Weihua Li, Mingjun Yang, Zhijun Zhou
Summary: The study showed that flurochloridone induces apoptosis in TM4 cells through the mitochondrial apoptotic pathway, accompanied by accumulation of ROS, depolarization of the mitochondrial membrane potential, etc. Pretreatment with the ROS scavenger NAC significantly alleviated flurochloridone-induced cell apoptosis and MMP depolarization.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Chemistry, Multidisciplinary
Jaime Martin, Enrique Gomez-Bengoa, Alexandre Genoux, Cristina Nevado
Summary: A catalytic method for synthesizing a variety of cyclometalated (C^N)gold(III) complexes is reported. The unprecedented Rh-to-Au(III) transmetalation allows for the easy transfer of (C^N) ligands between the two metals in a redox-neutral process. The reaction uses commercially available precursors and proceeds under mild and environmentally friendly conditions. Experimental and computational studies support a multi-step transmetalation mechanism from rhodium to gold as the underlying process for these transformations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Jiwei Wang, Kemeng Yuan, Gendi Wang, Ye Liu, Jun Zhang
Summary: 3,4-Diphenyl isoquinoline and 2,3-diphenyl indole were synthesized by catalytic selective bis-arylative endo cyclization of gold acetylides. The approach was also extended to prepare six-membered mesoionic NHC complexes, leading to 1,3-N-heterocyclic dicarbene (NHDCs) Au-2 and Au/Ag complexes. Key intermediates were isolated and studied for their reactivity towards coupling partners, supporting proposed mechanisms.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Barbara Pascucci, Francesca Spadaro, Donatella Pietraforte, Chiara De Nuccio, Sergio Visentin, Paola Giglio, Eugenia Dogliotti, Mariarosaria D'Errico
Summary: Cockayne syndrome group A is characterized by sun sensitivity and neurodevelopmental abnormalities. Excessive oxidative stress and mitochondrial fragmentation in CS-A cells are associated with hyperactivation of DRP1. Inhibition of DRP1 leads to reduction in reactive oxygen and nitrogen species, improvement in mitochondrial integrity, and decrease in apoptosis, suggesting DRP1 as a potential target for CS patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Inorganic & Nuclear
Andrea Pettenuzzo, Keti Vezzu, Maria Luisa Di Paolo, Eirini Fotopoulou, Luciano Marchio, Lisa Dalla Via, Luca Ronconi
Summary: The study developed and characterized four organometallic gold(III)-dithiocarbamato glycoconjugates as potential anticancer agents, showing antiproliferative effects against ovarian carcinoma cells in low micromolar range. Mechanistic studies revealed their capability to act as topoisomerase inhibitors and disrupt mitochondrial membrane integrity, leading to cell death through the generation of ROS and promotion of oxidative stress.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Medicinal
Yuhan Yuan, Yuanyuan Zhang, Jing Chen, Chunxia Huang, Haimei Liu, Wenlong Li, Lijuan Liang, Yi Wang, Yunjun Liu
Summary: A new ligand DTOIP was synthesized and combined with three iridium(III) complexes to form Ir1, Ir2, and Ir3. The complexes showed high antiproliferative activity against B16 cells by inducing apoptosis through mitochondrial entry, decreasing glutathione levels, increasing intracellular ROS content, and causing DNA damage. In vivo experiments demonstrated that Ir1 effectively inhibits tumor growth.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Juzheng Zhang, Yanping Li, Ronghao Fang, Wei Wei, Yong Wang, Jiamin Jin, Feng Yang, Jian Chen
Summary: Metal compounds, especially gold complexes, have attracted attention as possible therapeutics for lung cancer. This review summarizes examples of anticancer gold(I) and gold (III) complexes for lung cancer treatment and discusses their mechanisms of action and approaches to improve their efficiency.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yu-Lan Li, Xiao-Min Zhu, Hong Liang, Chris Orvig, Zhen-Feng Chen
Summary: This review provides a summary of recent progress in ASGPR and GAR-mediated and/or pH-responsive HCC-targeted drug delivery. Multifunctional DDS may enhance anticancer effects, reduce side effects, but further research is needed in investigating MDR of HCC.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Medicine, Research & Experimental
Xing Lu, Hong Liang, Chris Orvig, Zhen-Feng Chen
Summary: Mcl-1, a member of the Bcl-2 family of proteins, plays a key role in regulating the intrinsic pathway of apoptosis and is correlated with cancer progression and drug resistance. Developing inhibitors of Mcl-1 is essential for effective cancer therapy.
CURRENT MOLECULAR MEDICINE
(2021)
Article
Chemistry, Inorganic & Nuclear
Luke Wharton, Elena Kurakina, Valery Radchenko, Paul Schaffer, Chris Orvig
Summary: This study compared two structurally related potentially nonadentate chelating ligands to examine the influence of bifunctionalization on their coordination chemistry and metal ion selectivity. Improved synthetic routes were developed for each compound, and radiolabeling studies showed significant differences in their affinity for large radiometal ions. Nuclear magnetic resonance spectroscopy and density functional theory calculations were used to explore the coordination chemistry and conformational analysis of each metal complex. Theoretical simulations revealed notable differences in coordination geometry and denticity, which explained the observed selectivity in metal binding.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Thomas Kostelnik, Hayden Scheiber, Rosita Cappai, Neha Choudhary, Felix Lindheimer, Maria de Guadalupe Jaraquemada-Pelaez, Chris Orvig
Summary: A family of phosphonate-bearing chelators was synthesized and studied for their potential in metal-based (radio)-pharmaceuticals. Both experimental and theoretical approaches were used to investigate the complexation of these ligands with metal ions, highlighting important factors affecting stability constants and structural confirmation.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Neha Choudhary, Hayden Scheiber, Jiale Zhang, Brian O. Patrick, Maria de Guadalupe Jaraquemada-Pelaez, Chris Orvig
Summary: A new octadentate chelator H(4)HBEDpa has been investigated for its chelation properties with trivalent metal ions, showing high metal-sequestering capacity for Fe3+ and susceptibility to hydrolysis for Ga3+ at higher pH. Density functional theory (DFT) calculations validated experimental findings, demonstrating tight binding of Fe(HBEDpa)- in an asymmetric pattern and the formation of octadentate complexes with larger metal ions like Lu3+.
INORGANIC CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Hou-Tian Yan, Rui-Xue Liu, Qi-Zhen Yang, Yan-Cheng Liu, Hong-Chang Li, Rui-Feng Guo, Lin-Hua Wu, Li-Min Liu, Hong Liang
Summary: A new complex, EFX-Ca, was synthesized by reacting enrofloxacin with Ca(II). The study showed that EFX-Ca had lower toxicity and better therapeutic effects in bacteria and zebrafish.
Article
Chemistry, Inorganic & Nuclear
Aidan Ingham, Luke Wharton, Tarek El Sayed, Lily Southcott, Brooke L. McNeil, Maria B. Ezhova, Brian O. Patrick, Maria de Guadalupe Jaraquemada-Pelaez, Chris Orvig
Summary: A new chelator H(2)ampa was designed and synthesized as a potential radiopharmaceutical chelator. The study investigated its coordination behavior with radioactive metals and found that H(2)ampa can effectively coordinate Bi3+, Pb2+, and La3+ ions to form metal complexes, demonstrating its potential application in radiopharmaceutical labeling.
INORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Qi-Zhen Yang, Hong-Chang Li, Zhong-Bao Guo, Yong-Zhi Liao, Rui-Xue Liu, Yan-Cheng Liu, Hong Liang
Summary: DA-Cu exhibits significant antibacterial activity against Flavobacterium columnar, the bacteria causing gill-rot disease in fish. Moreover, the therapeutic effect of DA-Cu at a lower dosage is superior to DA and the positive control Sanhuang San.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Ruixue Liu, Jingbo Cui, Tongyan Ding, Yancheng Liu, Hong Liang
Summary: This review focuses on the metal complexes of polycyclic aromatic hydrazones and summarizes their biological activities, particularly their antibacterial and anticancer properties. The potential in structural design and biological activity of these complexes remains to be explored. More attention should be paid to this promising area of research.
Article
Crystallography
Qianjun Deng, Zitian Tang, Ruixue Liu, Yuan Liu, Huaxuan Liang, Yancheng Liu
Summary: This article presents a new rhodium complex and investigates its intercalative binding ability with DNA. The complex forms a six-coordinate distorted octahedral coordination geometry and shows higher binding ability compared to a typical DNA intercalator. This study provides important insights into the interaction between coordination compounds and DNA.
Article
Chemistry, Physical
Jia-long Tian, Hou-tian Yan, Qin Hu, Rui-xue Liu, Li-min Liu, Yan-cheng Liu
Summary: Enrofloxacin (EFX) was used to synthesize two transition metal complexes for the purpose of examining their crystal structures and antibacterial activities. The crystal structures of EFX-Mn and EFX-Co were found to belong to the same monoclinic crystal system with a six-coordinated octahedral configuration. In vitro antibacterial tests showed that both complexes exhibited significant growth inhibitory effects against pathogenic bacteria, particularly showing stronger bactericidal effects against E. coli and S. typhi compared to EFX itself.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Chemistry, Inorganic & Nuclear
Lily Southcott, Chris Orvig
Summary: 8-Hydroxyquinoline is a versatile compound with impressive metal chelating abilities, utilized in various fields such as medicine, nuclear medicine, and nanotechnology. Recent research has focused on its potential to chelate larger radiometal ions with longer half-lives and different indications.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Inorganic & Nuclear
Aidan Ingham, Thomas Kostelnik, Brooke L. McNeil, Brian O. Patrick, Neha Choudhary, Maria De Guadalupe Jaraquemada-Pelaez, Chris Orvig
Summary: Amide-based chelators DTPAm, EGTAm, and ampam were synthesized and studied for their coordination properties with [Pb-nat/203]Pb2+ ions using H-1 NMR spectroscopy and X-ray diffraction. Results showed that DTPAm exhibited higher stability and activity, making it a promising candidate for [Pb-203/212]Pb2+-based radiopharmaceutical applications, while EGTAm and ampam showed lower performance and were deemed unsuitable for similar applications.
DALTON TRANSACTIONS
(2021)
Article
Endocrinology & Metabolism
Yunyun Di, Ellen K. Wasan, Jacqueline Cawthray, Jaweria Syeda, Munawar Ali, David M. L. Cooper, Ahmad Al-Dissi, Nima Ashjaee, Wubin Cheng, James Johnston, David M. Weekes, Thomas I. Kostelnik, Chris Orvig, Kishor M. Wasan
Summary: In this study, the efficacy and toxicity of a novel lanthanum compound, La (XT), in an ovariectomized rat model of osteoporosis were evaluated. The treatment did not show kidney or liver toxicities, and increased trabecular bone stiffness.
Article
Chemistry, Multidisciplinary
Neha Choudhary, Kendall E. Barrett, Manja Kubeil, Valery Radchenko, Jonathan W. Engle, Holger Stephan, Maria De Guadalupe Jaraquemada-Pelaez, Chris Orvig
Summary: The study investigated the affinity of the bisoxine hexadentate chelating ligand H(3)glyox for Mn2+, Cu2+, and Lu3+ ions, revealing different thermodynamic stabilities of the three metal complexes with Cu2+ being the highest and Mn2+ the lowest. DFT calculations showed distinct geometries and coordination preferences of these metal ions in the complexes, with potential implications for further investigations in Mn-52g/55-based bimodal imaging.
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)
