Design and Synthesis of New Dual Binding Site Cholinesterase Inhibitors:in vitroInhibition Studies within silicoDocking.
Cholinesterases (ChEs) play a vital role in the regulation of cholinergic transmission. The inhibition of ChEs is considered to be involved in increasing acetylcholine level in the brain and thus has been implicated in the treatment of Alzheimer's disease. We have designed and synthesized a series of novel indole derivatives and screened them for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of the tested compounds exhibited inhibitory activity against AChE and BChE. Among them4fand6eshowed the highest AChE inhibitory activity with IC5091.21±0.06 and 68.52±0.04 μM, respectively. However compound5aexhibited the highest inhibitory activity against BChE (IC5055.21±0.12 μM).
Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore, 54000, Pakistan.
Muhammad
M
Yar
Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Pasteura 1, Poland and Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Cracow, Medyczna 9, Poland.
Marek
M
Bajda
Department of Chemistry, Government College University, Lahore, 54000, Pakistan.
Rana Atif
RA
Mehmood
Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore, 54000, Pakistan.
Lala Rukh
LR
Sidra
Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran, 31261, Saudi Arabia.
Nisar
N
Ullah
Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore, 54000, Pakistan.
Lubna
L
Shahzadi
Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan.
Muhammad
M
Ashraf
Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan.
Tayaba
T
Ismail
Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan.
Sohail Anjum
SA
Shahzad
Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore, 54000, Pakistan.
Zulfiqar Ali
ZA
Khan
Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore, 54000, Pakistan.
Syed Ali Raza
SA
Naqvi
Department of Allied Sciences and Chemical Pathology, University of Health Sciences, Lahore, 54600, Pakistan.
Nasir
N
Mahmood
Acetylcholinesterase; Alzheimer’s disease; Butyrylcholinesterase; Hydrazides; Indole derivatives; Molecular docking; SAR.