17702-83-9Relevant academic research and scientific papers
Design, synthesis and insecticide activity of novel acetylcholinesterase inhibitors: Triazolinone and phthalimide heterodimers
Xie, Ruliang,Mei, Xiangdong,Ning, Jun
, p. 345 - 350 (2019)
Based on the “cluster effect” and the structure characters of acetylcholinesterase (AChE; EC 3.1.1.7), a new series of 1,2,4-triazolin-3-one and phthalimide heterodimers were designed, synthesized, and evaluated as potent dual acetylcholinesterase inhibitors (AChEIs). Most of the synthesized compounds showed good in vitro inhibitory activities towards both Drosophila melanogaster acetylcholinesterase (DmAChE) and Musca domestica acetylcholinesterase (MdAChE). Among them, 5g was found to be the most potent anti-AChE de-rivate (5g, IC50=8.07μM to DmAChE, IC50=32.24μM to MdAChE). It was 2.31- and 1.35-fold more active than the positive control ethion (CP, IC50=18.62μM to DmAChE, IC50=43.56μM to MdAChE). The docking model study revealed that 5g possessed the fitted spatial structure and bound to the central pocket and peripheral site of DmAChE. Moreover, most compounds demonstrated high insecticidal activity to Lipaphis erysimi and Tetranychus cinnabarinus at the concentration of 300mg/L.
Design, synthesis and evaluation of novel 2-(Aminoalkyl)-isoindoline-1,3- dione derivatives as dual-binding site acetylcholinesterase inhibitors
Ignasik, Michalina,Bajda, Marek,Guzior, Natalia,Prinz, Michaela,Holzgrabe, Ulrike,Malawska, Barbara
, p. 509 - 516 (2012)
A new series of 2-(diethylaminoalkyl)-isoindoline-1,3-dione derivatives intended as dual binding site cholinesterase inhibitors were designed using molecular modeling and evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and the formation of the β-amyloid (Aβ) plaques. For AChE inhibitory activity, the spectrophotometric method of Ellman and the electrophoretically mediated microanalysis assay were used, giving good results. Most of the synthesized compounds had AChE inhibitory activity with IC50 values ranging from IC50 = 0.9 to 19.5 μM and weak Aβ anti-aggregation inhibitory activity. These results support the outcome of docking studies which tested compounds targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The most promising selective AChE inhibitors are compounds 10 (IC50 = 1.2 μM) and 11 (IC50 = 1.1 μM), with 6-7 methylene chains, which also inhibit Aβ fibril formation. A new series of 2-(diethylaminoalkyl)-isoindoline-1,3- dione derivatives intended as dual-binding site cholinesterase inhibitors were designed using molecular modeling. They were evaluated as inhibitors of acetylcholinesterase, butyrylcholinesterase, and the formation of β-amyloid (Aβ) plaques. The most promising selective AChE inhibitors are compounds 10 (IC50 = 1.2 μM) and 11 (IC50 = 1.1 μM), with 6-7 methylene chains, which also inhibit Aβ fibril formation. Copyright
Strategic engineering of alkyl spacer length for a pH-tolerant lysosome marker and dual organelle localization
Bhowal, Rohit,Biswas, Suprakash,Chopra, Deepak,Dutta, Tanoy,Koner, Apurba L.,Silswal, Akshay
, p. 9630 - 9644 (2021)
Long-term visualization of lysosomal properties is extremely crucial to evaluate diseases related to their dysfunction. However, many of the reported lysotrackers are less conducive to imaging lysosomes precisely because they suffer from fluorescence quenching and other inherent drawbacks such as pH-sensitivity, polarity insensitivity, water insolubility, slow diffusibility, and poor photostability. To overcome these limitations, we have utilized an alkyl chain length engineering strategy and synthesized a series of lysosome targeting fluorescent derivatives namelyNIMCsby attaching a morpholine moiety at theperiposition of the 1,8-naphthalimide (NI) ring through varying alkyl spacers between morpholine and 1,8-naphthalimide. The structural and optical properties of the synthesizedNIMCswere explored by1H-NMR, single-crystal X-ray diffraction, UV-Vis, and fluorescence spectroscopy. Afterward, optical spectroscopic measurements were carefully performed to identify a pH-tolerant, polarity sensitive, and highly photostable fluoroprobes for further live-cell imaging applications.NIMC6displayed excellent pH-tolerant and polarity-sensitive properties. Consequently, allNIMCswere employed in kidney fibroblast cells (BHK-21) to investigate their applicability for lysosome targeting and probing lysosomal micropolarity. Interestingly, a switching of localization from lysosomes to the endoplasmic reticulum (ER) was also achieved by controlling the linker length and this phenomenon was subsequently applied in determining ER micropolarity. Additionally, the selected probeNIMC6was also employed in BHK-21 cells for 3-D spheroid imaging and inCaenorhabditis elegans(C. elegans) forin vivoimaging, to evaluate its efficacy for imaging animal models.
Synthesis and activity studies of N-[ω-N'-(adamant-1'-yl)aminoalkyl]-2-(4'-dimethylaminophenyl)acetamides: In the search of selective inhibitors for the different molecular forms of acetylcholinesterase
Perola, Emanuele,Cellai, Luciano,Brufani, Mario
, p. 575 - 580 (1998)
A series of N-[ω-N'-(adamant-1'-yl)aminoalkyl]-2-(4'-dimethylaminophenyl)acetamides were synthesized and tested as acetylcholinesterase inhibitors. A significant selectivity toward acetylcholinesterases from various natural sources, mainly differing in th
Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors
Si, Weijie,Zhang, Tao,Zhang, Lanxiang,Mei, Xiangdong,Dong, Mengya,Zhang, Kaixin,Ning, Jun
, p. 2380 - 2382 (2016)
A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44 nM and 13.58 nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study.
Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents
Luo, Wen,Wang, Ting,Hong, Chen,Yang, Ya-Chen,Chen, Ying,Cen, Juan,Xie, Song-Qiang,Wang, Chao-Jie
, p. 17 - 26 (2016)
A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced β-amyloid (Aβ) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. The derivatives showed potent self-induced Aβ aggregation inhibition and peroxyl radical absorbance activity. Moreover, compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Thus, these compounds could become multifunctional agents for further development for the treatment of AD.
Potent acetylcholinesterase inhibitors: Design, synthesis, and structure - Activity relationships of bis-interacting ligands in the galanthamine series
Mary, Aude,Renko, Dolor Zafiarisoa,Guillou, Catherine,Thal, Claude
, p. 1835 - 1850 (1998)
New galanthamine derivatives, especially bis-interacting ligands 3-5 and 7-9 were prepared in order to interact with the catalytic and the peripheral sites of acetylcholinesterase (AChE). The synthesis, the anticholinesterase activities, and the structure-activity relationships of bis-interacting ligands are reported. Compounds 4d-e were found to be more potent than galanthamine and tacrine in inhibiting AChE. Copyright (C) 1998 Elsevier Science Ltd.
Antibacterial alkylguanidino ureas: Molecular simplification approach, searching for membrane-based MoA
Ardino, Claudia,Botta, Lorenzo,D'Agostino, Ilaria,Docquier, Jean-Denis,Dreassi, Elena,Filippi, Silvia,Lucidi, Massimiliano,Petricci, Elena,Poggialini, Federica,Poli, Giulio,Rango, Enrico,Sannio, Filomena,Visaggio, Daniela,Visca, Paolo
supporting information, (2022/02/16)
The ever-faster rise of antimicrobial resistance (AMR) represents a major global Public Health challenge. New chemical entities with innovative Modes of Action (MoAs) are thus desirable. We recently reported the development of a novel class of broad-spectrum bactericidal agents, the AlkylGuanidino Ureas (AGU). Due to their polycationic structure, they likely target bacterial membranes. In order to better understand their MoA, we synthesized a library of AGU derivatives by structural simplification of selected hit compounds and developed specific assays based on membrane models by means of both analytical and computational techniques. Cell-based assays provided experimental evidence that AGUs disrupt bacterial membranes without showing hemolytic behavior. Hence, we herein report a thorough chemical and biological characterization of a new series of AGUs obtained through molecular simplification, allowing the rational design of potent antibacterial compounds active on antibiotic-resistant strains.
Catalytic remote hydrohalogenation of internal alkenes
Chen, Pinhong,Jin, Jianbo,Li, Xiang,Liu, Guosheng
, (2022/02/07)
Primary alkyl halides have broad utility as fine chemicals in organic synthesis. The direct halogenation of alkenes is one of the most efficient approaches for the synthesis of these halides. Internal alkenes, in particular mixtures of isomers from refine
Synthesis and Antileishmanial Evaluation of Arylimidamide-Azole Hybrids Containing a Phenoxyalkyl Linker
Abdelhameed, Ahmed,Feng, Mei,Joice, April C.,Zywot, Emilia M.,Jin, Yiru,La Rosa, Chris,Liao, Xiaoping,Meeds, Heidi L.,Kim, Yena,Li, Junan,McElroy, Craig A.,Wang, Michael Zhuo,Werbovetz, Karl A.
, p. 1901 - 1922 (2021/02/22)
Due to the limitations of existing medications, there is a critical need for new drugs to treat visceral leishmaniasis. Since arylimidamides and antifungal azoles both show oral activity in murine visceral leishmaniasis models, a molecular hybridization approach was employed where arylimidamide and azole groups were separated by phenoxyalkyl linkers in an attempt to capitalize on the favorable antileishmanial properties of both series. Among the target compounds synthesized, a greater antileishmanial potency against intracellular Leishmania donovani was observed as the linker length increased from two to eight carbons and when an imidazole ring was employed as the terminal group compared to a 1,2,4-triazole group. Compound 24c (N-(4-((8-(1H-imidazol-1-yl)octyl)oxy)-2-isopropoxyphenyl) picolinimidamide) displayed activity against L. donovani intracellular amastigotes with an IC50 value of 0.53 μM. When tested in a murine visceral leishmaniasis model, compound 24c at a dose of 75 mg/kg/day p.o. for five consecutive days resulted in a modest 33% decrease in liver parasitemia compared to the control group, indicating that further optimization of these molecules is needed. While potent hybrid compounds bearing an imidazole terminal group were also strong inhibitors of recombinant CYP51 from L. donovani, as assessed by a fluorescence-based assay, additional targets are likely to play an important role in the antileishmanial action of these compounds.
