Article
Chemistry, Medicinal
Sarah Preston, Jose Garcia-Bustos, Liam G. Hall, Sheree D. Martin, Thuy G. Le, Abhijit Kundu, Atanu Ghoshal, Nghi H. Nguyen, Yaqing Jiao, Banfeng Ruan, Lian Xue, Fei Huang, Bill C. H. Chang, Sean L. McGee, Timothy N. C. Wells, Michael J. Palmer, Abdul Jabbar, Robin B. Gasser, Jonathan B. Baell
Summary: A series of novel compounds were synthesized as potent inhibitors of Haemonchus contortus, the parasitic nematode of sheep, showing high selectivity in mammalian cell lines but causing acute toxicity in rodents, possibly due to respiratory inhibition. Additionally, potent cytotoxicity was observed in rat hepatocytes, unrelated to toxicity in respiring cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lin Zhang, Yiming Chen, Fahui Li, Lihui Zhang, Jinhong Feng, Lei Zhang
Summary: Histone deacetylases (HDACs) are important targets for the development of anticancer drugs. The 5-chloro-4-((substituted phenyl)amino)pyrimidine fragment plays a crucial role in the structure of HDAC inhibitors. Compound L20 exhibited selective inhibition against HDAC1, HDAC2, and HDAC3, while showing lower activity against HDAC6. It also demonstrated inhibitory effects on both hematological and solid cancers by promoting cell cycle arrest and apoptosis.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yanle Zhi, Hongmei Li, Pei Yang, Qiaomei Jin, Chao Yao, Baoquan Li, Jun Ling, Hao Guo, Tonghui Li, Jianlin Jin, Yue Wang, Yadong Chen, Tao Lu, Shuai Lu
Summary: In recent years, FLT3 has been identified as an exciting target for AML treatment. However, resistance to FLT3 inhibitors caused by acquired point mutations in the tyrosine kinase domain (TKD) has limited their efficacy. Compound LT-540-717 (32) has been discovered as a potent FLT3 inhibitor with inhibitory activity against multiple acquired FLT3 mutations. It also exhibits antiproliferative activity against FLT3-mutation driven cells and shows potential as a new anti-AML drug.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Hae Jin Kee, Inkyeom Kim, Myung Ho Jeong
Summary: This article provides an overview of the pathogenesis of hypertension, current anti-hypertensive drugs, and the need for novel drugs. It focuses on the role and regulatory mechanisms of HDACs in hypertension and discusses the progress in developing HDAC inhibitors as potential therapeutic targets.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Tingting Lin, Jiacheng Li, Liping Liu, Yuanqing Li, Hualiang Jiang, Kaixian Chen, Pan Xu, Cheng Luo, Bing Zhou
Summary: Cyclin-dependent kinases are important targets for cancer therapy, but most potent CDK inhibitors lack selectivity. A newly synthesized compound, DC-K2in212, showed high potency and selectivity towards CDK2, with effective anti-proliferative activity and low toxicity on normal cells. Further studies revealed that DC-K2in212 suppressed CDK2-associated signaling, blocked cell cycle progression, and induced cellular apoptosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shun Tu, Ting-Jian Zhang, Yi Zhang, Xu Zhang, Zhen-Hao Zhang, Fan-Hao Meng
Summary: This study synthesized two series of amide-based XO inhibitors, with compound 3i showing the most promising in vitro inhibitory potency and hypouricemic effect. Molecular simulations provided insights into the interaction modes of representative compounds, supporting compound 3i as a lead for further exploration of amide-based XO inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yatao Huang, Shuai Li, Youde Wang, Zhiwei Yan, Yachun Guo, Liying Zhang
Summary: In this study, the protective effect of compound 1 against astrocyte H/R injury was investigated by targeting PYGB. Results show that compound 1 does not alleviate astrocytes H/R injury after PYGB knockdown. It also does not improve cellular energy metabolism or inhibit apoptosis-associated protein expression. This study provides new insights into the mechanism of compound 1's efficacy.
Review
Biochemistry & Molecular Biology
Svetlana Demyanenko, Valentina Dzreyan, Svetlana Sharifulina
Summary: Cerebral ischemia is the second leading cause of death worldwide, requiring multimodal stroke therapy. Histone deacetylase inhibitors have shown to be effective in protecting the brain from ischemic damage by inducing neurogenesis and angiogenesis in damaged brain areas, promoting functional recovery after stroke.
Article
Agriculture, Multidisciplinary
Zhibing Wu, Hyung-Yeon Park, Dewen Xie, Jingxin Yang, Shuaitao Hou, Nasir Shahzad, Chan Kyung Kim, Song Yang
Summary: This study investigated a series of novel SDH inhibitors for their antifungal activity against phytopathogenic fungi, showing that some compounds exhibited excellent antifungal activity. Experiment results further revealed that these compounds might work by targeting SDH.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yatao Huang, Shuai Li, Youde Wang, Zhiwei Yan, Yachun Guo, Liying Zhang
Summary: Compound 1 is a novel brain-type glycogen phosphorylase inhibitor with protective effects on ischemic brain injury. It alleviates hypoxic-ischemic injury in astrocytes by improving cell viability and reducing LDH leakage, intracellular glucose content, and post-ischemic ROS level. It also improves cellular energy metabolism, reduces anaerobic glycolysis, and inhibits apoptosis.
Article
Agricultural Engineering
Xuefeng Lu, Tae Kyung Hyun
Summary: Post-translational histone modifications, such as histone acetylation, play key roles in regulating gene expression in plant growth, development, and stress responses. The research found that HDAC inhibitors led to hyperacetylation of histone H3, enhancing MeJA-induced ginsenoside production in ginseng adventitious roots. Additionally, the study identified specific PgHDACs that may serve as crucial factors in controlling MeJA-induced ginsenoside production.
INDUSTRIAL CROPS AND PRODUCTS
(2021)
Review
Oncology
Amandine Badie, Christian Gaiddon, Georg Mellitzer
Summary: Our understanding of the identity of many cancers has greatly increased in recent years, leading to progress in early detection and treatment options. However, gastric cancer remains poorly treated with low survival rates. The lack of possibilities for early detection and the variations between tumors of gastric cancer patients are major challenges. Histone Deacetylases (HDACs) have been identified to be potentially related to gastric cancer. In this review, we summarize the current knowledge on the role of HDACs in gastric cancer development and their potential as early detection markers and targets for new treatment options.
Article
Chemistry, Physical
Kayed Abu-Safieh, Musa El-Barghouthi, Monther A. Khanfar, Bader A. Salameh, Islam S. Al-Aqrabawi, Baker Jawabrah Al Hourani, Basem F. Ali
Summary: The title compound with three independent molecules in the asymmetric unit forms a compact 3D supramolecular structure through hydrogen bonding. Molecular docking techniques were used to study interactions with proteins and interpret cytotoxic activities against cancer cell lines. Strong interactions were observed between the title compound and a closely related structure with modifications at position 5 in the pyrazole ring.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Chemistry, Multidisciplinary
Jingxin Yang, Dewen Xie, Chengzhi Zhang, Cailong Zhao, Zhibing Wu, Wei Xue
Summary: Inspired by the application of amides in plant pathogens, novel pyrazole carboxamide derivatives were designed and synthesized, showing broad-spectrum antifungal activities. One compound exhibited excellent activities against fungi in vitro and in vivo, and mechanistic study results provided a new perspective for further research on this class of compounds.
ARABIAN JOURNAL OF CHEMISTRY
(2022)
Review
Oncology
Fengyi Guo, Hongjing Wang
Summary: This review summarizes the classification and mechanisms of action of histone deacetylase and the clinical application of their inhibitors in ovarian cancer. Histone deacetylase inhibitors show promising potential as anti-cancer drugs, and combination therapy with other anticancer drugs for synergistic effects can improve efficacy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)