Article
Chemistry, Organic
Petr Jansa, Ivan Barvik, Daniela Hulcova, Eliska Matousova
Summary: In this study, polycyclic compounds with N-methyl substitution, structurally related to Amaryllidaceae alkaloids, were synthesised. Two approaches, N-oxidation and Boc protection of the nitrogen, were investigated to avoid interference of the nitrogen lone electron pair with the reaction sequence. The products prepared showed higher activity against BuChE than AChE, indicating a need for larger ligands in future studies.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Physical
Jing -Jing Qian, Jing-Pei Zou, Shan-Ming Liu, Xiao-Qing Zhang, Rui Li, Zhao-Yuan Zhang, Wei-Weil Liu, Shao-Jie Ma, Da-Hua Shi
Summary: A series of 2-phenylthiazole derivatives were synthesized and characterized as cholinesterase inhibitors. Compound 5a showed the most potent inhibitory effect on acetylcholinesterase, comparable to the drug donepezil. Molecular docking and simulations revealed its stable interaction with the peripheral anion site of acetylcholinesterase. Compound 5a holds promise as a lead compound for further research and development in Alzheimer's disease.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
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
Biochemistry & Molecular Biology
Alma Marisol Ramirez-Ruiz, Martha Elena Avila-Cossio, Arturo Estolano-Cobian, Jose Manuel Cornejo-Bravo, Ana Laura Martinez, Ivan Cordova-Guerrero, Bibiana Roselly Cota-Ramirez, Krysta Paola Carranza-Ambriz, Ignacio A. Rivero, Aracely Serrano-Medina
Summary: In this study, we synthesized seven new compounds and discovered that one of them exhibited significant acetylcholinesterase inhibitory activity and improved cognitive function in animal experiments. These results contribute to the design of new drugs for treating cognitive disorders.
Article
Plant Sciences
Lin -Yu Huang, Jin-Bu Xu, Xiang-Yu Li, Hai-Ning Song, Lin Chen, Xian-Li Zhou, Feng Gao
Summary: Pd(OAc)(2)/NiXantphos efficiently catalyzes the direct arylation at the C-14 position of matrine, leading to the synthesis of various arylmatrine derivatives that exhibit enhanced insecticidal effects.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Plant Sciences
Jinliang Li, Fengchao Li, Guoxing Wu, Furong Gui, Hongmei Li, Lili Xu, Xiaojiang Hao, Yuhan Zhao, Xiao Ding, Xiaoping Qin
Summary: In this study, two new sesquiterpenes were isolated from Laggera pterodonta, along with six known eudesmane-type sesquiterpenes, and their inhibitory effect on acetylcholinesterase (AChE) was characterized. The results showed that these compounds had a dose-dependent inhibitory effect on AChE, with compound 5 exhibiting the highest inhibitory activity. Additionally, all compounds showed certain levels of toxicity on C. elegans and displayed good ADMET properties.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Jorge Estevez, Marina Terol, Miguel Angel Sogorb, Eugenio Vilanova
Summary: Phenyl valerate (PV) is a neutral substrate used to measure the activity of neuropathy target esterase (NTE) and has been shown to be hydrolyzed by both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). Kinetic studies revealed that the interaction between PV and AChE does not follow the classic competition model, and it was found that acetylthiocholine (AtCh) can enhance PVase activity at low concentrations but inhibit it at high concentrations. This suggests that products released at the active site play a role in the hydrolysis reactions of different substrates.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Physical
Chun Zhang, Yi-Tao Sun, Li-Xin Gao, Bo Feng, Xue Yan, Xue-Hui Guo, Ai-Min Ren, Yu-Bo Zhou, Jia Li, Wen-Long Wang
Summary: The study designed and synthesized five 2-phenyl-1,3,4-thiadiazole derivatives, with the representative compound PT10 showing good inhibitory activity and fluorescence response against SHP1, indicating potential applications in the integration of diagnosis and treatment.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Xu Han, Yun Long Yu, Duo Ma, Zhao Yan Zhang, Xin Hua Liu
Summary: The study synthesized 66 2-phenyl-4H-chromone derivatives with potential telomerase inhibitory activity, with compound A33 showing significant inhibition. A33 was found to arrest cell cycle at G2/M phase and induce apoptosis in a concentration-dependent manner, while also reducing dyskerin expression.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Narasimha Pullaguri, Andrea R. Kagoo, Anamika Bhargava
Summary: The antimicrobial agent triclosan can inhibit the activity of acetylcholinesterase (AChE) both by direct binding and indirectly through increased oxidative stress, resulting in neurotoxicity.
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, Applied
Matheus Ardenghi Peixoto, Lucilia Kato, Cecilia Maria Alves de Oliveira, Boniek Gontijo, Cleuza Conceicao da Silva, Armando Mateus Pomini, Luiz C. Klein-Junior, Carolina dos Santos Passos, Amelia T. Henriques, Geanderson Bannwart, Silvana Maria de Oliveira Santin
Summary: Aspidosperma macrocarpon, commonly known as 'guatambu' or 'peroba', is found across North America to South America and in Brazil. Two indole alkaloids, kopsanone (1) and unreported N(4)-oxide-kopsanone (2), were isolated from the leaves of A. macrocarpon.
NATURAL PRODUCT RESEARCH
(2021)
Article
Engineering, Environmental
Annamalai Yamuna, Natarajan Karikalan, Jun-Hee Na, Tae Yoon Lee
Summary: This study presents a rapid and sensitive electrochemical detection method for carbaryl (CRBL) based on a pyrochlore-type lanthanum tin oxide (LSO) nanoparticles (NPs) modified screen-printed carbon electrode (SPCE). The LSO NPs/SPCE exhibited good electroanalytical performance for CRBL detection, with low detection limit and high selectivity among interfering pesticides. The sensor showed high recovery in detecting CRBL in soil, water, and vegetable samples, proving its suitability for rapid detection of CRBL.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Sen -sen Hu, Ting-jian Zhang, Zhao-ran Wang, En-yu Xu, Qiu-yin Wang, Xu Zhang, Shuai Guo, Jing Wang, Fan-hao Meng
Summary: Previous studies indicated that N-phenyl aromatic amides are a promising class of xanthine oxidase (XO) inhibitors. In this study, a series of N-phenyl aromatic amide derivatives were designed and synthesized to establish their structure-activity relationship. The most potent XO inhibitor identified was N-(3-(1H-imidazol1-yl)-4-((2-methylbenzyl)oxy)phenyl)-1H-imidazole-4-carboxamide (12r), which displayed comparable in vitro potency to topiroxostat. Molecular docking and simulation revealed strong interactions between 12r and specific residues. In vivo hypouricemic studies demonstrated improved uric acid lowering effects of 12r. Pharmacokinetic studies showed a short half-life of 0.25 h after oral administration, and 12r exhibited noncytotoxicity against normal cells.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Julia Lisa-Molina, Pedro Gomez-Murillo, Irene Arellano-Martin, Carles Jimenez, Maria L. Rodriguez-Escobar, Luciana R. Tallini, Francesc Viladomat, Laura Torras-Claveria, Jaume Bastida
Summary: Amaryllidaceae alkaloids, found in Narcissus species, have medicinal properties and potential for treating cholinergic disorders like Alzheimer's disease. The production of galanthamine, an Amaryllidaceae alkaloid used in AD treatment, is insufficient to meet the demand. This study aims to improve galanthamine production and explore new drugs for AD treatment. Additionally, the alkaloid content and AChE inhibitory activity of less-studied autumn-flowering Narcissus species were evaluated.