Article
Biochemistry & Molecular Biology
Margarita E. Neganova, Ekaterina V. Smirnova, Elena V. Sharova, Oleg I. Artyushin, Yulia R. Aleksandrova, Ekaterina Yu. Yandulova, Natalia S. Nikolaeva, Valery K. Brel
Summary: By using click chemistry, a method for synthesizing unique conjugates based on sesquiterpene lactones, namely dehydrocostuslactone and alantolactone, has been developed. The length of the 1,2,3-triazole spacer was varied to expand the structural range of the conjugates. It was found that conjugates based on alantolactone with a long spacer and those containing dehydrocostuslactone with a short spacer exhibited the greatest cytotoxic effect, possibly by causing dissipation of the transmembrane potential of mitochondria and inhibiting glycolysis.
Review
Chemistry, Medicinal
Haoyang Huang, Qing He, Binghua Guo, Xudong Xu, Yinjuan Wu, Xuerong Li
Summary: Drug repurposing is a feasible strategy in developing novel medications, and antiparasitic drugs have shown potential in cancer treatment with diverse mechanisms. Further exploration in clinical trials and modifications in drug delivery systems or combinations are recommended for future research.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Yu-De Chu, Siew-Na Lim, Chau-Ting Yeh, Wey-Ran Lin
Summary: COX5B is a potential biomarker associated with unfavorable prognosis in colorectal cancers (CRCs). It promotes cell growth and attenuates drug susceptibility in CRCs cells through modulating CLDN2 expression.
Article
Oncology
Junjie Lan, Octavia Cadassou, Cyril Corbet, Olivier Riant, Olivier Feron
Summary: The study demonstrates the feasibility of efficiently screening for mitochondrial complex I inhibitors based on the ability of drug candidates to induce L-lactate release. Drug candidates identified showed complex I inhibitory activity and potential radiosensitizing effects in tumor-mimicking conditions, indicating promising anticancer properties.
Article
Immunology
Joseph W. George, Jane E. Mattingly, Nashanthea J. Roland, Cassandra M. Small, Benjamin G. Lamberty, Howard S. Fox, Kelly L. Stauch
Summary: The study found that DTG and FTC had different effects on mitochondrial function in HeLa and BV2 cells, suggesting that cell type-specific metabolic changes may contribute to the toxic side effects of these ARV drugs.
FRONTIERS IN IMMUNOLOGY
(2021)
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
Biochemistry & Molecular Biology
Yuting Zheng, Andrew A. Gibb, Hongkai Xu, Siqi Liu, Bradford G. Hill
Summary: In this study, we investigated the composition and abundance of mitochondrial supercomplexes in murine cardiac mitochondria. We found that the provision of respiratory substrates and the alteration of the cardiac glucose-fatty acid cycle can influence the levels of supercomplexes. Our findings suggest that the energetic state of the heart plays a regulatory role in supercomplex assembly and stability.
Article
Neurosciences
Marisa A. Jeffries, Lauren E. McLane, Luipa Khandker, Marie L. Mather, Angelina V. Evangelou, Divyangi Kantak, Jennifer N. Bourne, Wendy B. Macklin, Teresa L. Wood
Summary: This study investigated the role of mTOR signaling in oligodendrocyte lineage during remyelination. The results showed that mTOR is required for metabolic function in cuprizone-demyelinated adult brain, influencing myelin production efficiency and myelin thickness during the repair process. Loss of mTOR in OPCs did not affect remyelination efficiency after other types of lesions, suggesting a specific function in cuprizone-induced demyelination.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Cardiac & Cardiovascular Systems
Wusheng Xiao, William M. Oldham, Carmen Priolo, Arvind K. Pandey, Joseph Loscalzo
Summary: Inflammatory mediators such as TNF alpha and lipopolysaccharide significantly impact the metabolism of endothelial cells, enhancing glycolysis, mitochondrial oxidative phosphorylation, and the pentose phosphate pathway. Inflammation promotes a metabolic shift to glycolysis in endothelial cells, while enhancement of oxidative phosphorylation and the pentose phosphate pathway suppresses inflammation.
CIRCULATION RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Jubayer Rahman, Parul Singh, Nicolas S. Merle, Nathalie Niyonzima, Claudia Kemper
Summary: The complement system, as an unexpected, cell-autonomous orchestrator of normal cell physiology, controls key pathways of metabolism during immune cell homeostasis and effector function. Little is known about the exact structure and localization of intracellular complement components, but they do interact closely with mitochondria, impacting metabolism significantly.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Andreia Faria-Pereira, Vanessa A. Morais
Summary: The brain is one of the most energy-consuming organs in the body, and synaptic transmission is a major contributor to this energy consumption. The brain primarily uses glucose for energy, which is metabolized through glycolysis and/or mitochondrial oxidative phosphorylation. This review examines the balance between glycolysis and oxidative phosphorylation in meeting synaptic energy demands. Dysregulation of synaptic bioenergetics is increasingly associated with neurodegenerative disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Nick Schoenmann, Nicholas Tannenbaum, Ryan M. Hodgeman, Raghavan Pillai Raju
Summary: Dichloroacetate (DCA), a naturally occurring xenobiotic, has been used as an investigational drug for over 50 years. It serves primarily as a pyruvate dehydrogenase kinase inhibitor, reversing the preference for glycolysis over oxidative phosphorylation and increasing available energy. This review examines the potential and clinical application of DCA in various diseases including cancer, metabolic disorders, cerebral ischemia, trauma, and sepsis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Biology
Rafael A. Casuso, Saad Al Fazazi, Julio Plaza-Diaz, Francisco J. Ruiz-Ojeda, Ascension Rueda-Robles, Jeronimo Aragon-Vela, Jesus R. Huertas
Summary: The study showed that consuming 4.61 mg/kg/d of hydroxytyrosol during exercise can increase the mRNA expression of important metabolic proteins, but does not lead to higher protein content.
Article
Food Science & Technology
Sulaiman K. Matarneh, Con-Ning Yen, Jocelyn Bodmer, Samer W. El-Kadi, David E. Gerrard
Summary: This study aimed to test mitochondrial functionality under conditions simulating postmortem metabolism using an in vitro model. The results showed that mitochondria can mobilize pyruvate generated through glycolysis in conditions simulating muscle postmortem metabolism.
Article
Neurosciences
Rajiv Sainath, Gianluca Gallo
Summary: NGF induces the development of axonal filopodia and branches by activating the PI3K-Akt signaling pathway through the TrkA receptor. The initiation and steady state phases of the PI3K-Akt signaling pathway have different dependencies on cellular energy metabolism pathways, such as oxidative phosphorylation and glycolysis. The initiation phase of PI3K and Akt signaling is associated with the localization of mitochondria, while the steady state phase may involve contributions from mitochondria, glycolysis, and endocytosed signalosomes.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Chemistry, Applied
Xiaopeng Peng, Yang Yang, Bingling Luo, Shijun Wen, Peng Huang
Summary: A diverse set of fluorenes can be conveniently constructed starting from cyclic diaryliodoniums and terminal alkenes through Pd-catalyzed reactions. These reactions involve a conventional Mizoroki-Heck reaction and a reductive Heck reaction, with a general scope of alkenes leading to the synthesis of 29 fluorenes, expanding the structural diversity of fluorenes.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Oncology
Shijie Ma, Zizheng Dong, Qingbin Cui, Jing-Yuan Liu, Jian-Ting Zhang
Summary: eIF3i is a subunit of the eIF3 complex involved in translation initiation of mRNAs. Apart from its role in global translational control, eIF3i may individually regulate translation of specific mRNAs, participate in signaling pathways, and influence cellular processes.
Article
Biochemistry & Molecular Biology
Silpa Narayanan, Nehaben A. Gujarati, Jing-Quan Wang, Zhuo-Xun Wu, Jagadish Koya, Qingbin Cui, Vijaya L. Korlipara, Charles R. Ashby, Zhe-Sheng Chen
Summary: The study showed that the novel benzamide derivative VKNG-2 can reverse MDR caused by overexpression of ABCG2 transporter in colon cancer cells; VKNG-2 significantly improves the efficacy of anticancer drugs in vitro and works by inhibiting the efflux function of the ABCG2 transporter.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Yang Yang, Yalin Tu, Junfeng Lu, Qiuhe Chen, Zeyu Zhu, Weijia Peng, Wenbo Zhu, Shijun Wen, Ji Zhang, Wei Yin, Rongbiao Pi
Summary: This study discovered a novel multi-kinase inhibitor, PT109, which suppressed the proliferation, colony formation, and migration of GBM cells, and reprogrammed them into oligodendrocytes. Proteomic analysis showed that PT109 influenced energy metabolism, cell cycle, and immune system processes of GBM-associated proteins. Metabolomic analysis revealed that PT109 improved the aerobic respiration process in glioma cells. Overall, PT109 provided a new strategy for the development of anti-glioma drugs by reprogramming GBM and changing its metabolic pattern through the PTBP1/PKM1/2 pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Tian Tian, Shengyi Zhang, Bingling Luo, Feng Yin, Wenhua Lu, Yiqing Li, Kezhi Huang, Qiao Liu, Peng Huang, G. Garcia-Manero, Shijun Wen, Yumin Hu
Summary: In this study, a benzoimidazole compound was identified as a selective treatment for FLT3/ITD leukemia. The compound HP1328, derived from the benzoimidazole scaffold, demonstrated desirable properties and significantly reduced leukemia burden and prolonged survival in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Hui Peng, Qian Liu, Yameng Sun, Bingling Luo, Tianyian Yu, Peng Huang, Daqian Zhu, Shijun Wen
Summary: In this study, it was demonstrated that linear unsymmetrical diaryliodoniums can undergo one-pot cyclization/arylation using a dual nickel/palladium metal system, and the in situ generated benzoxazole motifs can be utilized as directing groups for subsequent C-H activated arylation from the unwanted aryl iodide, exhibiting good atom economy and regioselectivity.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Oncology
Peiting Zeng, Wenhua Lu, Jingyu Tian, Shuang Qiao, Jiangjiang Li, Christophe Glorieux, Shijun Wen, Hui Zhang, Yiqing Li, Peng Huang
Summary: The study found that overexpressed wild-type IDH2 in AML promoted leukemia cell survival and proliferation by facilitating the conversion of alpha-KG to isocitrate/citrate for lipid synthesis. Inhibition of wild-type IDH2 resulted in reduced lipid synthesis, decreased c-Myc expression downregulated by alpha-KG, and inhibition of AML viability and proliferation. Pharmacological inhibition of IDH2 showed therapeutic effects in AML cells with wild-type IDH2, inducing downregulation of C-MYC in vivo.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Zhirong Guo, Yameng Sun, Liyun Liang, Wenhua Lu, Bingling Luo, Zhouming Wu, Bitao Huo, Yumin Hu, Peng Huang, Qiang Wu, Shijun Wen
Summary: This study presents the design, synthesis, and biological evaluation of first-in-class dual EZH2/BRD4 inhibitors. The most promising compound, YM458, demonstrates potent inhibitory activity against EZH2 and BRD4 and remarkable antiproliferative capacity against various solid cancer cell lines. In vivo experiments validate the therapeutic potential of EZH2/BRD4 dual inhibitors in lung cancer and pancreatic cancer xenograft tumor models, highlighting their potential to target a broad scope of resistant solid tumors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Fang Liu, Xuan Wang, Jianli Duan, Zhijie Hou, Zhouming Wu, Lingling Liu, Hanqi Lei, Dan Huang, Yifei Ren, Yue Wang, Xinyan Li, Junxiao Zhuo, Zijian Zhang, Bin He, Min Yan, Huiming Yuan, Lihua Zhang, Jinsong Yan, Shijun Wen, Zifeng Wang, Quentin Liu
Summary: This study introduces a PROTAC cocktail that effectively degrades AURKA in acute myeloid leukemia cells, inhibits AML stem cells, and induces AML regression in mouse models and primary patient cells. This spatial-temporal drug administration strategy shows promise in eliminating the multifaceted functions of oncoproteins and preventing cancer stem cell-mediated drug resistance.
Article
Biochemistry & Molecular Biology
Qingbin Cui, Wenwen Ding, Panpan Liu, Bingling Luo, Jing Yang, Wenhua Lu, Yumin Hu, Peng Huang, Shijun Wen
Summary: This study demonstrates that enhancing the mitochondria-targeting capacity of gold compounds can enhance their efficacy in eradicating cancer cells. Bi-gold compounds showed better suppression of cancer cell proliferation compared to mono-gold compounds, and the most potent compound, BGC2a, inhibited the antioxidant enzyme TrxR and increased cellular ROS. BGC2a accumulated within mitochondria, leading to mitochondrial dysfunction and inhibition of tumor growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Multidisciplinary
Xiaopeng Peng, Abdur Rahim, Weijie Peng, Feng Jiang, Zhenhua Gu, Shijun Wen
Summary: This article summarizes the recent advances in the research field of cyclic aryliodoniums, including their design and synthetic applications. The general preparation of typical diphenyl iodoniums, construction of heterocyclic iodoniums and monoaryl iodoniums are described. The use of cyclic aryliodoniums as initiators for cascade reactions and the construction of complex structures such as polycycles and biaryls are discussed. Furthermore, the recent advance of cyclic aryliodoniums as halogen-bonding organocatalysts is described.
Article
Chemistry, Medicinal
Jenny Beebe, Sophia Josephraj, Chao J. Wang, Jacob Danielson, Qingbin Cui, Caoqinglong Huang, Lincoln Barlow, Ryan H. Zhang, Taolan Zhang, Harikrishna Nakshatri, Zizheng Dong, Xiaohong Li, Jing-Yuan Liu, Jian-Ting Zhang
Summary: Fatty acid synthase (FASN) is overexpressed in cancer and not in normal tissues, and proton pump inhibitors (PPIs), approved for digestive disorders, have been found to inhibit FASN with anticancer activities. Metabolites of PPIs may contribute to the lasting anticancer effects by inhibiting FASN.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Plant Sciences
Xiaozhuo Tan, Meiling Le, Haiwen Wang, Bitao Huo, Tiantian Yu, Peng Huang, Tiangang Luan, Shijun Wen
Summary: This study reports the design and synthesis of novel peptide-drug conjugates (PDCs) that bind to both the extracellular and intracellular domains of epidermal growth factor receptor (EGFR). One peptide motif interacts with the extracellular domain, while the other motif derived from an EGFR inhibitor occupies the intracellular kinase domain. Among the synthetic PDCs, compound 14c shows the best inhibition of EGFR phosphorylation and the ability to inhibit cell proliferation and colony formation in lung cancer cells. This study provides a novel strategy to develop more potent EGFR inhibitors by targeting both extracellular and intracellular domains simultaneously.
PHYTOCHEMISTRY LETTERS
(2023)
Article
Medicine, Research & Experimental
Jing-Quan Wang, Qingbin Cui, Zi-Ning Lei, Qiu-Xu Teng, Ning Ji, Lusheng Lin, Zhijun Liu, Zhe-Sheng Chen
Summary: This study constructed and validated a homology model for human MRP7 based on cryo-EM structures, obtained structure-function relationship of MRP7 from molecular dynamics simulations and docking studies, discussed motion patterns correlated with efflux mechanism, and described predicted substrate- and modulator-binding sites of MRP7 for the first time.
