Article
Biochemistry & Molecular Biology
Jatinder Vir Singh, Shubham Thakur, Nitish Kumar, Harjeet Singh, Venus Singh Mithu, Harpreet Singh, Kavita Bhagat, Harmandeep Kaur Gulati, Anchal Sharma, Harbinder Singh, Sahil Sharma, Preet Mohinder Singh Bedi
Summary: In this study, a series of multitargeting molecules were rationally designed and synthesized to develop anti-Alzheimer's agents. Compound 4b showed multitargeting properties as an effective and well-tolerated anti-Alzheimer's agent in vivo. It exhibited acetylcholinesterase inhibition, DNA protection against oxidative damage, and inhibition of A beta(1-42) aggregations. Molecular dynamics simulations confirmed the stability of the compound with the enzyme. In animal experiments, compound 4b and donepezil both significantly improved memory. The study suggests that compound 4b, designed based on the structural features of donepezil, has potential as an alternative therapeutic for Alzheimer's disease.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Blazej Grodner, Mariola Napiorkowska, Dariusz Maciej Pisklak
Summary: This study evaluated the inhibition efficacy of four aminoalkanol derivatives on acetylcholinesterase in vitro. The results showed that the inhibitory potency of the derivatives varied depending on the nature of the substituents, with isopropylamine and/or methyl substituents being the most effective. Docking studies suggested that the compounds bind to the peripheral anionic site rather than entering the catalytic pocket.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Aysan Etemadi, Salar Hemmati, Mohammad Shahrivar-Gargari, Yasaman Tamaddon Abibiglue, Ahad Bavili, Maryam Hamzeh-Mivehroud, Siavoush Dastmalchi
Summary: Indanone derivatives with meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed as cholinesterase inhibitors based on the structures of donepezil and ebselen analogs. The synthesized compounds showed inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC50 values ranging from 0.12 to 11.92 μM and 0.04 to 24.36 μM, respectively. The most potent AChE inhibitor was compound 5c, belonging to the meta-substituted compounds, while the most active BChE inhibitor was para-substituted derivative 7b. The introduced indanone-aminopropoxy benzylidenes have potential for drug discovery against Alzheimer's disease.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Chemistry, Multidisciplinary
Begum Nurpelin Saglik, Serkan Levent, Derya Osmaniye, Asaf Evrim Evren, Abdullah Burak Karaduman, Yusuf Ozkay, Zafer Asim Kaplancikli
Summary: Alzheimer's disease is a progressive neurological disorder that affects memory and cognitive function in the elderly. This study focused on the chemical structure of donepezil and designed 42 novel derivatives. The compounds D28-D30 and D37-D39 showed promising antioxidant, enzyme inhibition, and plaque inhibition activities, suggesting their potential in treating AD symptoms and providing palliative care.
Article
Chemistry, Medicinal
Raquel B. M. de Almeida, Deyse B. B. Barbosa, Mayra R. R. do Bomfim, Jessika A. O. Amparo, Bruno S. S. Andrade, Silvia L. L. Costa, Joaquin M. Campos, Jorddy N. Cruz, Cleydson B. R. Santos, Franco H. A. Leite, Mariana B. B. Botura
Summary: The compound ZINC390718 was found to exhibit inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and showed low cytotoxicity in vitro. Molecular dynamics (MD) simulation revealed that ZINC390718 interacted with the catalytic residue sites of both enzymes. These findings suggest that ZINC390718 could be a potential chemotype for the development of new dual cholinesterase inhibitors.
Article
Biochemistry & Molecular Biology
Nafisah M. Al-Rifai, Nemeh M. Al-Khalileh, Jalal A. Zahra, Musa I. El-Barghouthi, Fouad H. Darras
Summary: A library of N-benzylpyridinium-based compounds was synthesized and evaluated for their acetylcholinesterase inhibitory activity and antioxidant activity. The benzyl and fluoro derivatives exhibited the highest inhibitory activity and showed potential as potential drug candidates.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
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
Biochemistry & Molecular Biology
Marco Paolino, Mariagrazia Rullo, Samuele Maramai, Modesto de Candia, Leonardo Pisani, Marco Catto, Claudia Mugnaini, Antonella Brizzi, Andrea Cappelli, Massimo Olivucci, Federico Corelli, Cosimo D. Altomare
Summary: Neurodegenerative diseases are complex disorders characterized by protein misfolding, oxidative stress, and neuroinflammation, resulting in neuronal loss and cognitive dysfunction. In this study, the researchers designed and synthesized a library of cinnamic acid-inspired compounds that can modulate their activity under light irradiation. These compounds showed selective inhibition of acetylcholinesterase and monoamine oxidase B, which are associated with Alzheimer's disease. Molecular docking studies were conducted to understand the differences in inhibitory potency between the E and Z diastereomers of the best-performing compound. These findings provide a potential avenue for the development of innovative multitarget photo-switch drugs for neurodegenerative diseases.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Plant Sciences
Jin-Bu Xu, Shi-Xing Miao, Feng Gao, Lin-Xi Wan
Summary: A series of arylated huperzine A derivatives were efficiently synthesized through late-stage modification of huperzine A using the Suzuki-Miyaura cross-coupling reaction. The acetylcholinesterase inhibitory activity of the synthesized compounds was evaluated, and it was found that introducing aryl groups at the C-1 position resulted in unsatisfactory activity. The study highlights the importance of the pyridone carbonyl group for maintaining the anti-acetylcholinesterase potency of huperzine A.
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
(2023)
Article
Chemistry, Medicinal
Thierno Moussa Ndongo, Marieta L. C. Passos, Fernando Duraes, Diana I. S. P. Resende, Madalena Pinto, Emilia Sousa, Maria Lucia M. F. S. Saraiva
Summary: A miniaturized microsequential injection/lab-on-valve (mu SIA-LOV) system has been developed as a useful alternative for inhibitory studies on acetylcholinesterase, showing potential inhibitory effects higher than clinical agents at lower costs and reagent consumption. The system is robust, rapid, reliable, and easy to use.
ARCHIV DER PHARMAZIE
(2021)
Article
Biochemistry & Molecular Biology
Bhupinder Kumar, Ashish Ranjan Dwivedi, Tania Arora, Khadga Raj, Vikash Prashar, Vijay Kumar, Shamsher Singh, Jyoti Prakash, Vinod Kumar
Summary: This study reports a series of N-propargyl-substituted diphenylpyrimidine derivatives with potential inhibitory activity against AChE and MAO-B, as well as neuroprotective effects and improvement of cognitive function.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Rosa Purgatorio, Nicola Gambacorta, Francesco Samarelli, Gianfranco Lopopolo, Modesto de Candia, Marco Catto, Orazio Nicolotti, Cosimo D. Altomare
Summary: This study explores the impact of the malonamide bridge on the enzyme inhibition potency of peptidomimetic inhibitors of coagulation factor Xa (fXa). Through the synthesis and testing of 23 malonamide derivatives, it was found that the malonamide linker significantly increases the anti-fXa potency and selectivity. Some of these compounds also show potential as neuroprotective agents for the treatment of Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Georgios Papagiouvannis, Panagiotis Theodosis-Nobelos, Eleni A. Rekka
Summary: Alzheimer's Disease is a neurodegenerative disorder characterized by memory loss and cognitive impairment. Current treatment options only alleviate symptoms, and effective treatments have not been obtained yet. In this study, a series of compounds with significant antioxidant and/or anti-inflammatory activity were identified, which could potentially be developed as multi-targeting agents against Alzheimer's Disease.
Article
Chemistry, Medicinal
Yichun Shi, Heng Zhang, Qing Song, Guangjun Yu, Zhuoling Liu, Feng Zhong, Zhenghuai Tan, Xiuxiu Liu, Yong Deng
Summary: Based on the multitarget-directed ligands approach, a series of 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives were designed, synthesized, and evaluated as innovative multifunctional agents against Alzheimer's disease. Compound 12a showed significant inhibition of AChE and anti-A beta activity, as well as potential antioxidant, metal chelation, and anti-neuroinflammation properties. In vivo studies demonstrated that 12a effectively ameliorated cognitive dysfunction in scopolamine-treated mice by regulating the cholinergic system and oxidative stress simultaneously.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biology
Aravinda Babu, Mathew John, M. J. Liji, E. Maria, S. J. Bhaskar, B. K. Binukmar, Ayyiliath M. Sajith, Eeda Koti Reddy, K. V. Dileep, K. Sunil
Summary: Human acetylcholinesterase (hAChE) plays a potential role in acetylcholine management and AChE inhibitors have a significant impact in therapeutics. This study explored the active site geometry of hAChE upon binding to different ligands and discovered two prominent sub-pockets near the active site. Structural bioinformatics analysis identified 132 putative sub-pockets focused tacrine derivatives (SPFTDs) that showed stronger binding affinity than tacrine. The identification of these sub-pockets and SPFTDs provides new possibilities for future drug discovery targeting AChE in the treatment of Alzheimer's disease (AD).
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Xiao Xie, Xiao-Meng Li, Fangfei Qin, Jianwei Lin, Gong Zhang, Jingyi Zhao, Xiucong Bao, Rongfeng Zhu, Haiping Song, Xiang David Li, Peng R. Chen
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2017)
Article
Chemistry, Medicinal
Ling Huang, Zonghua Luo, Feng He, Anding Shi, Fangfei Qin, Xingshu Li
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2010)
Article
Chemistry, Inorganic & Nuclear
Zonghua Luo, Fangfei Qin, Shilei Yan, Xingshu Li
TETRAHEDRON-ASYMMETRY
(2012)
Article
Chemistry, Multidisciplinary
Huixin Luo, Wei Tang, Hongyu Liu, Xiangmei Zeng, William Shu Ching Ngai, Rui Gao, Heyun Li, Ran Li, Huangtao Zheng, Jianting Guo, Fangfei Qin, Gang Wang, Kexin Li, Xinyuan Fan, Peng Zou, Peng R. Chen
Summary: The interactions between RNA and proteins are crucial for cellular processes. This study developed a photocatalytic crosslinking strategy combined with mass spectrometry and RNA sequencing to study the composition and dynamics of protein-RNA interactions. The approach identified numerous RNA binding proteins in human cells and investigated the dynamic changes of RBPs in macrophage cells and their interactions with SARS-CoV-2 RNA.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Hui Wang, Boyuan Li, Linyu Zuo, Bo Wang, Yan Yan, Kai Tian, Rong Zhou, Chenlu Wang, Xizi Chen, Yongpeng Jiang, Haonan Zheng, Fangfei Qin, Bin Zhang, Yang Yu, Chao-Pei Liu, Yanhui Xu, Juntao Gao, Zhi Qi, Wulan Deng, Xiong Ji
Summary: This study reveals that AAA+ ATPase RUVBL2 co-occupies promoters with Pol II and different transcription factors, promoting RPB1 CTD clustering and transcription initiation. Depletion of RUVBL2 leads to a decrease in Pol II clusters and inhibits RNA synthesis, while tethering RUVBL2 to active promoters enhances Pol II clustering. Target genes directly linked to the RUVBL2-Pol II axis are identified, many of which are involved in cancer and cellular functions.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Fangfei Qin, Boyuan Li, Hui Wang, Sihui Ma, Jiaofeng Li, Shanglin Liu, Linghao Kong, Huangtao Zheng, Rongfeng Zhu, Yu Han, Mingdong Yang, Kai Li, Xiong Ji, Peng R. Chen
Summary: We developed a strategy named SiTomics for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations. Our SiTomics toolkit revealed distinct crotonylation and β-hydroxybutyrylation upon short chain fatty acids stimulation and established linkages for chromatin acylation mark-defined proteome, genome, and functions. SiTomics offers a plat-form technology for elucidating the metabolites-modification-regulation axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones.
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)
