TY - JOUR
T1 - Exploring indole-based-thiadiazole derivatives as potent acetylcholinesterase and butyrylcholinesterase enzyme inhibitors
AU - Taha, Muhammad
AU - Rahim, Fazal
AU - Uddin, Nizam
AU - Khan, Ihsan Ullah
AU - Iqbal, Naveed
AU - Anouar, El Hassane
AU - Salahuddin, Mohammed
AU - Farooq, Rai Khalid
AU - Gollapalli, Mohammed
AU - Khan, Khalid Mohammed
AU - Zafar, Ameeduzzafar
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Indole based thiadiazole derivatives (1–18) were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The IC50 values of the synthesized analogues ranging between 0.17 ± 0.05 to 33.10 ± 0.6 μM against (AChE) and 0.30 ± 0.1 to 37.60 ± 0.6 μM against (BChE) enzymes. Among the series compounds 8 (IC50 = 0.17 ± 0.05 μM) (IC50 = 0.30 ± 0.1 μM), 9 (IC50 = 0.30 ± 0.05 μM) (IC50 = 0.60 ± 0.05 μM) and 10 (IC50 = 1.30 ± 0.1 μM) (IC50 = 2.60 ± 0.1) were found to be the most potent analogues bearing para, ortho, and meta-fluoro substitutions on phenyl ring attached to thiadiazole. In addition, all the synthesized scaffolds were characterized by using 1H NMR, 13C NMR spectroscopy, and high-resolution Mass Spectrometry (HR-MS). To apprehend the binding mode of interaction of the most potent synthesized derivatives, a molecular docking study was performed.
AB - Indole based thiadiazole derivatives (1–18) were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The IC50 values of the synthesized analogues ranging between 0.17 ± 0.05 to 33.10 ± 0.6 μM against (AChE) and 0.30 ± 0.1 to 37.60 ± 0.6 μM against (BChE) enzymes. Among the series compounds 8 (IC50 = 0.17 ± 0.05 μM) (IC50 = 0.30 ± 0.1 μM), 9 (IC50 = 0.30 ± 0.05 μM) (IC50 = 0.60 ± 0.05 μM) and 10 (IC50 = 1.30 ± 0.1 μM) (IC50 = 2.60 ± 0.1) were found to be the most potent analogues bearing para, ortho, and meta-fluoro substitutions on phenyl ring attached to thiadiazole. In addition, all the synthesized scaffolds were characterized by using 1H NMR, 13C NMR spectroscopy, and high-resolution Mass Spectrometry (HR-MS). To apprehend the binding mode of interaction of the most potent synthesized derivatives, a molecular docking study was performed.
KW - Acetylcholinesterase
KW - Butyrylcholinesterase
KW - Indole-based-thiadiazole
UR - http://www.scopus.com/inward/record.url?scp=85114818889&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2021.08.065
DO - 10.1016/j.ijbiomac.2021.08.065
M3 - Article
C2 - 34390751
AN - SCOPUS:85114818889
SN - 0141-8130
VL - 188
SP - 1025
EP - 1036
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -