Article
Biochemistry & Molecular Biology
Fan Yang, Jiangang Zhao, Guang Chen, Hao Han, Shuang Hu, Ningwei Wang, Junqin Wang, Yuzhen Chen, Zihao Zhou, Baozhu Dai, Yunlei Hou, Yajing Liu
Summary: Alzheimer's disease (AD) is characterized by neuronal loss, plaque and neurofibrillary tangle formation, and disturbed neuronal Ca2+ homeostasis, which cause severe dementia, memory loss, and cognitive and behavioral abnormalities. Calcium dysregulation and low acetylcholine levels play important roles in AD progression. In this study, dantrolene derivatives were identified as dual inhibitors of the ryanodine receptor and AChE, and compound 22a showed excellent inhibitory potency against both SOICR and AChE. Furthermore, compound 22a demonstrated therapeutic effects in AD model mice by improving memory, cognitive behavior, and synaptic strength. These findings suggest that these dantrolene derivatives could serve as potential chemical entities for AD treatment.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Kamilia M. Amin, Doaa E. Abdel Rahman, Heba Abdelrasheed Allam, Haidy H. El-Zoheiry
Summary: Twenty novel 7-benzyloxycoumarin based compounds were synthesized using a variety of bioactive chemical fragments, some of which showed remarkable acetylcholinesterase inhibitory activity even better than donepezil. Kinetic study and in vivo evaluation confirmed their potential anti-Alzheimer's disease effects.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Wen-Long Wu, Ze-Yu Wen, Jing-Jing Qian, Jing-Pei Zou, Shan-Ming Liu, Shun Yang, Tian Qin, Qun Yang, Yu-Han Liu, Wei-Wei Liu, Jing Wang, Li-Ying Shi, Da-Hua Shi
Summary: In this study, a series of hybrids of benzimidazole and 1,3,5-triazine were designed, synthesized, and evaluated as multi-target agents for the treatment of Alzheimer's disease. Compound 9f exhibited excellent acetylcholinesterase inhibitory activity, stable interaction with acetylcholinesterase, good metal chelating properties, and drug similarity, indicating its potential as a multi-target agent for Alzheimer's disease treatment.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Medicinal
Wenjie Liu, Limeng Wu, Wenwu Liu, Liting Tian, Huanhua Chen, Zhongchan Wu, Nan Wang, Xin Liu, Jingsong Qiu, Xiangling Feng, Zihua Xu, Xiaowen Jiang, Qingchun Zhao
Summary: MTDLs, such as compound 30, have shown promising potential as therapeutic options for Alzheimer's disease. Compound 30, a novel coumarin derivative, exhibits multi-target inhibitory effects on AChE, BuChE, GSK-3 beta, and BACE1. It also shows moderate cytotoxicity and good blood-brain barrier permeability. Compound 30 has the characteristics of a competitive AChE inhibitor and shows potential as a multifunctional candidate for AD therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Shoaib Manzoor, Moustafa T. Gabr, Bisma Rasool, Kavita Pal, Nasimul Hoda
Summary: The study reported a new series of deoxyvasicinone analogues as dual inhibitors of acetylcholinesterase (AChE) and tau aggregation, demonstrating their potential as multitargeted ligands for Alzheimer's disease. Among the synthesized compounds, one particular compound showed significant inhibition of AChE activity and cellular tau oligomerization, highlighting its promising potential for anti-AD drug development.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Aso Hameed Hasan, Sonam Shakya, Faiq H. S. Hussain, Sankaranarayanan Murugesan, Subhash Chander, Mohammad Rizki Fadhil Pratama, Shajarahtunnur Jamil, Basundhara Das, Subhrajit Biswas, Joazaizulfazli Jamalis
Summary: Acetylcholinesterase inhibitors are commonly prescribed medications for the treatment of Alzheimer's disease and dementia. In this study, a series of novel compounds were designed, synthesized, and tested for their ability to inhibit acetylcholinesterase activity. The results showed that these compounds exhibited significant inhibition and low cytotoxicity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Medicinal
Dan Liu, Honghua Zhang, Yuying Wang, Wencheng Liu, Gaofeng Yin, Degui Wang, Junfang Li, Tao Shi, Zhen Wang
Summary: This study designed and evaluated a series of carbamate derivatives as multifunctional therapeutic agents for Alzheimer's disease. Compound 1g exhibited dual inhibitory activity against AChE and BChE, reduced pro-inflammatory cytokine levels, increased anti-inflammatory cytokine levels, and inhibited the aggregation of A beta(1-42). It showed potential as a multi-functional therapeutic agent for further investigation in AD treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Meng-qiu Song, Wei Min, Jing Wang, Xi-Xi Si, Xiu-Jun Wang, Yu-Wei Liu, Da-Hua Shi
Summary: Twelve carbazole-coumarin hybrids were synthesized and compound 3h showed good AChE inhibitory activity. The structure-activity relationship studies revealed that the linker length and the structure of coumarin moieties affected the inhibitory activities of the hybrids on BuChE.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Sheunopa C. Mzezewa, Sylvester I. Omoruyi, Luke S. Zondagh, Sarel F. Malan, Okobi E. Ekpo, Jacques Joubert
Summary: The study synthesized and evaluated a series of 3,7-substituted coumarin derivatives for enzyme inhibitory activity and neuroprotective ability, with the compounds showing potential MAO-B inhibition activity and neuroprotective effects.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sukhvir Kaur, Yogita Bansal
Summary: Inhibition of both IL-6 and AChE is crucial for the treatment of Alzheimer's Disease (AD). This study identified the pharmacophores for IL-6 and AChE inhibition and designed novel molecules with dual inhibitory effects. Compound Y13g showed the strongest inhibitory activity and demonstrated dose-dependent effects in a mouse model.
BIOORGANIC CHEMISTRY
(2022)
Article
Food Science & Technology
Kudrat Randhawa, Varinder Singh, Sanimardeep Kaur, Ravinder Kaur, Suresh Kumar, Richa Shri
Summary: The study isolated resveratrol as the active constituent responsible for the antioxidant and anti-cholinesterase activities of the hydromethanol extract from Pleurotus florida. Resveratrol improved dementia and neurodegeneration in mice by reducing acetylcholinesterase action and oxidative stress, indicating its potential therapeutic effect for Alzheimer's disease.
FOOD SCIENCE AND HUMAN WELLNESS
(2021)
Article
Chemistry, Medicinal
Liping Guan, Dingxin Peng, Li Zhang, Jinjing Jia, Haiying Jiang
Summary: The marine environment is a rich source of functional materials, with seaweed containing potential compounds like liquiritigenin. In this study, derivatives based on liquiritigenin were synthesized and tested for their inhibitory effects on cholinesterases, showing potency against acetylcholinesterase and moderate to weak activity against butyrylcholinesterase. Kinetic studies revealed a dual binding site inhibition mechanism for compound 4o against AChE, and all tested compounds also displayed radical scavenging effects. The molecular docking simulation of 4o in the AChE active site correlated well with the pharmacological results.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Panpan Zhang, Ze Wang, Chenye Mou, Jiamei Zou, Yanfei Xie, Zhiwen Liu, C. Benjamin Naman, Yuechun Mao, Jiaxin Wei, Xinghan Huang, Jiahui Dong, Mengxiang Yang, Ning Wang, Haixiao Jin, Fufeng Liu, Dongdong Lin, Hao Liu, Fei Zhou, Shan He, Bin Zhang, Wei Cui
Summary: This study developed novel drug candidates that can inhibit AChE and Aβ(1-42) aggregation, demonstrating potential neuroprotective and cognitive-enhancing effects in mice.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Somaia S. Abd El-Karim, Manal M. Anwar, Nesreen S. Ahmed, Yasmin M. Syam, Samia A. Elseginy, Hanan F. Aly, Eman A. Younis, Wagdy K. B. Khalil, Kawkab A. Ahmed, Faten F. Mohammed, Maha Rizk
Summary: A series of novel benzofuran-based compounds were synthesized and investigated as acetylcholinesterase inhibitors. Compound 7c showed promising inhibitory activity and antioxidant activity, making it a potential candidate for the treatment of Alzheimer's disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Amina Benazzouz-Touami, Amina Chouh, Sabrina Halit, Souhila Terrachet-Bouaziz, Malika Makhloufi-Chebli, Karima Ighil-Ahriz, Artur M. S. Silva
Summary: A new set of hybrid derivatives containing pyrazole and coumarin scaffold were synthesized and evaluated for inhibitory activity against AChE and BuChE. Compounds 3e and 3f showed the highest AChE inhibitory activities, while compounds 3a and 3b were the best BuChE inhibitors. Molecular docking study and toxicity analysis suggested that these compounds have good oral bioavailability potential.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Medicinal
Huali Yang, Xiaobing Wang, Cheng Wang, Fucheng Yin, Lailiang Qu, Cunjian Shi, Jinhua Zhao, Shang Li, Limei Ji, Wan Peng, Heng Luo, Maosheng Cheng, Lingyi Kong
Summary: NUAK1, activated by LKB1, is a key component of the antioxidant stress response pathway and its inhibition suppresses colorectal tumor growth. Compound 9q, a derivative of WZ4003, shows strong inhibitory effects on NUAK1/2 enzyme activity and tumor cell proliferation, making it a potential candidate for further investigation as an anticancer drug.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Limei Ji, Lailiang Qu, Cheng Wang, Wan Peng, Shang Li, Huali Yang, Heng Luo, Fucheng Yin, Dehua Lu, Xingchen Liu, Lingyi Kong, Xiaobing Wang
Summary: The study demonstrates that piperlongumine analogue 6d shows potential antioxidant and anti-inflammatory activities in PC12 cells by activating the Nrf2 signaling pathway to combat oxidative stress. Further research indicates that 6d has the potential to be a therapeutic drug for neurodegenerative disorders related to oxidative stress and inflammation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Peng-Ran Cao, Yi-Lei Zheng, Yong-Qin Zhao, Xiao-Bing Wang, Hao Zhang, Mei-Hui Zhang, Ting Yang, Yu-Cheng Gu, Ming-Hua Yang, Ling-Yi Kong
Summary: Two novel natural products, beetleane A (1) and epicoane A (2), were isolated from the metabolites of an endophytic Epicoccum nigrum. Compound 1 features a unique beetlelike structure constructed by the fusion of an unusual [5.5.5.6]trioxafenestrane with a cycloheptane ring, while compound 2 possesses a compact cagelike structure with a unique 6/5/5/5/6/6/5 heptacyclic ring system. Both compounds exhibited strong antiliver fibrosis activity in vitro.
Article
Chemistry, Medicinal
Lailiang Qu, Limei Ji, Cheng Wang, Heng Luo, Shang Li, Wan Peng, Fucheng Yin, Dehua Lu, Xingchen Liu, Lingyi Kong, Xiaobing Wang
Summary: The selenium-containing compound 13f, based on ebselen and verubecestat, showed potential anti-Alzheimer's disease and antioxidant stress effects by reducing beta-amyloid production and alleviating oxidative stress. Furthermore, 13f also demonstrated anti-inflammatory and cytoprotective effects, making it a promising candidate for AD treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Shang Li, Lailiang Qu, Xiaobing Wang, Lingyi Kong
Summary: This review provides a comprehensive overview of the potential role of RIPK1 in the progression of Alzheimer's disease (AD). It explores the underlying linkages between RIPK1 and AD, including neuronal death, Aβ and Tau, inflammasome activation, BBB rupture, AMPK/mTOR, mitochondrial dysfunction, and O-glcNAcylation. The review also covers the discovery of RIPK1 inhibitors, ongoing clinical trials, and future RIPK1-targeted therapeutics.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Chemistry, Organic
Fucheng Yin, Wan Peng, Cheng Wang, Lailiang Qu, Xinye Chen, Lingyi Kong, Xiaobing Wang
Summary: A protocol for Rh(III)-catalyzed cascade reaction was established, which allows the efficient construction of phthalides and isocoumarins skeleton with broad applicability. The method can potentially be applied to the total synthesis of natural products.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Dehua Lu, Lailiang Qu, Cheng Wang, Heng Luo, Shang Li, Fucheng Yin, Xingchen Liu, Xinye Chen, Zhongwen Luo, Ningjie Cui, Wan Peng, Limei Ji, Lingyi Kong, Xiaobing Wang
Summary: Combining HDAC inhibitors with DNA damage agents has shown promise in treating solid tumors. We designed a series of harmine-based inhibitors, with compound 27 showing potential in binding to DNA and causing DNA damage. Compound 27 induced cell apoptosis through the p53 signaling pathway and exhibited significant anti-proliferation effects against HCT-116 cells.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Cheng Wang, Xinye Chen, Xingchen Liu, Dehua Lu, Shang Li, Lailiang Qu, Fucheng Yin, Heng Luo, Yonglei Zhang, Zhongwen Luo, Ningjie Cui, Lingyi Kong, Xiaobing Wang
Summary: EZH2 is often overexpressed in TNBC and other tumors, affecting tumor development and prognosis. The designed PROTACs molecule U3i precision targets EZH2 and shows good inhibitory effects on TNBC cells, inducing apoptosis without causing much damage to normal cells. U3i is a potential anticancer molecule for TNBC treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Fucheng Yin, Yifan Chen, Zhongwen Luo, Shang Li, Lingyi Kong, Xiaobing Wang
Summary: This study demonstrates the application of aryl halides in organic synthesis, specifically focusing on the usage of methyl 2-bromobenzoate and 2-nitrophenyl iodides as mild and effective bromination and iodination reagents. This efficient cascade catalysis method can be applied to the total synthesis of natural products Mafaicheenamine A and Claulamine A.
Article
Chemistry, Medicinal
Jiafu Leng, Yongjun Zhao, Ping Sheng, Yuanzheng Xia, Tingting Chen, Shifang Zhao, Shanshan Xie, Xiangyu Yan, Xiaobing Wang, Yong Yin, Lingyi Kong
Summary: The newly synthesized compound C3 exhibits potential anticancer activity by targeting tubulin to inhibit cancer cell proliferation and angiogenesis.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xinye Chen, Cheng Wang, Dehua Lu, Heng Luo, Shang Li, Fucheng Yin, Zhongwen Luo, Ningjie Cui, Lingyi Kong, Xiaobing Wang
Summary: Aberrant expression of EZH2 is frequently observed in cancers, but EZH2 inhibitors are not effective in treating solid tumors. Combination of EZH2 and BRD4 inhibitors may be a promising strategy. Therefore, a series of EZH2/BRD4 dual inhibitors were designed and synthesized. Compound 28 (KWCX-28) showed the most potential and inhibited cell proliferation, induced apoptosis, arrested cell cycle, and resisted H3K27ac upregulation. KWCX-28 is a potential dual EZH2/BRD4 inhibitor for treating solid tumors.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ningjie Cui, Shang Li, Yonglei Zhang, Fucheng Yin, Xinye Chen, Zhongwen Luo, Siyuan Wan, Xinxin Li, Lingyi Kong, Xiaobing Wang
Summary: This study synthesized and evaluated a series of structural analogues of Sibiriline and found that the optimal compound KWCN-41 can inhibit cell death, protect cell survival, and reduce inflammation levels. It is expected to be a potential drug for treating inflammatory diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Panhu Zhu, Tao Zhou, Hong Chen, Xingru Chen, Xiaobing Wang, Lingyi Kong, Minghua Yang
Summary: Triazoles have shown significant efficacy in treating fungal infections, but the increasing drug resistance limits their effectiveness. By designing well-crafted side chains, triazoles can have advantages such as higher potency and overcoming drug resistance. In this study, we synthesized fluconazole-core compounds and optimized their side chains to develop a potent antifungal agent, S-F24, which exhibited excellent broad-spectrum activity and maintained its effectiveness against multi-resistant Candida albicans.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Integrative & Complementary Medicine
Liu Xingchen, Wang Xiaobing
Summary: Parthenolide (PTL), derived from feverfew, has shown significant anticancer activity and has the potential to be a first-line drug. Structural modification strategies are recommended to enhance its anticancer activity. This review focuses on representative PTL derivatives and their mechanisms in cancer therapy.
CHINESE JOURNAL OF NATURAL MEDICINES
(2022)
Article
Chemistry, Medicinal
Dehua Lu, Cheng Wang, Lailiang Qu, Fucheng Yin, Shang Li, Heng Luo, Yonglei Zhang, Xingchen Liu, Xinye Chen, Zhongwen Luo, Ningjie Cui, Lingyi Kong, Xiaobing Wang
Summary: Aberrance of epigenetic modification is an important factor in hematological malignancies. There is promising potential in using HDAC and EZH2 dual inhibitors as a therapeutic strategy. Compound 20 exhibited excellent inhibitory activity against HDAC1 and EZH2, and also showed good antiproliferation activity against tumor cells, indicating its potential in treating hematological malignancies.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
