International Journal of Molecular Sciences (2019)
Update date:2022-09-26
Topics:
Bak, Andrzej
Kozik, Violetta
Kozakiewicz, Dariusz
Gajcy, Kamila
Strub, Daniel Jan
Swietlicka, Aleksandra
Stepankova, Sarka
Imramovsky, Ales
Polanski, Jaroslaw
Smolinski, Adam
Jampilek, Josef
A series of new benzene-based derivatives was designed, synthesized and comprehensively characterized. All of the tested compounds were evaluated for their in vitro ability to potentially inhibit the acetyl-and butyrylcholinesterase enzymes. The selectivity index of individual molecules to cholinesterases was also determined. Generally, the inhibitory potency was stronger against butyryl-compared to acetylcholinesterase; however, some of the compounds showed a promising inhibition of both enzymes. In fact, two compounds (23, benzyl ethyl(1-oxo-1-phenylpropan-2-yl)carbamate and 28, benzyl (1-(3-chlorophenyl)-1-oxopropan-2-yl) (methyl)carbamate) had a very high selectivity index, while the second one (28) reached the lowest inhibitory concentration IC50 value, which corresponds quite well with galanthamine. Moreover, comparative receptor-independent and receptor-dependent structure–activity studies were conducted to explain the observed variations in inhibiting the potential of the investigated carbamate series. The principal objective of the ligand-based study was to comparatively analyze the molecular surface to gain insight into the electronic and/or steric factors that govern the ability to inhibit enzyme activities. The spatial distribution of potentially important steric and electrostatic factors was determined using the probability-guided pharmacophore mapping procedure, which is based on the iterative variable elimination method. Additionally, planar and spatial maps of the host–target interactions were created for all of the active compounds and compared with the drug molecules using the docking methodology.
View MoreGeen Chemical Technology Co., Ltd
Contact:86-769-21660847
Address:1408, Yingfeng Commercial Center, Nancheng District
Nanjing Norris Pharm Technology Co., Ltd.
Contact:+86-13901585132
Address:2 Qiande Road, Jiangning sciencepark Hi-Tech Zone, Nanjing, P.R.China
Contact:+86-531-58668191 58668193 58668196 58661173
Address:No 55,Beixiaoxinzhuang West Street,Jinan City, Shandong Province
ZHEJIANG JIANYE CHEMICAL CO.,LTD.
Contact:86-571-64149273,64149234
Address:No. 48, Fuxi Road, Meicheng Town
Contact:+86-10-62651721
Address:29 Yongxing Road, Daxing District,Beijing China
Doi:10.1016/j.bmcl.2016.12.021
(2017)Doi:10.1016/j.tetlet.2006.10.064
(2006)Doi:10.1002/jhet.5570440504
(2007)Doi:10.1080/00397910008086940
(2000)Doi:10.1007/BF00958006
(1991)Doi:10.1023/A:1013111016841
(2001)