Exploring indole-based-thiadiazole derivatives as potent acetylcholinesterase and butyrylcholinesterase enzyme inhibitors

Muhammad Taha; Fazal Rahim; Nizam Uddin; Ihsan Ullah Khan; Naveed Iqbal; El Hassane Anouar; Mohammed Salahuddin; Rai Khalid Farooq; Mohammed Gollapalli; Khalid Mohammed Khan; Ameeduzzafar Zafar

doi:10.1016/j.ijbiomac.2021.08.065

Exploring indole-based-thiadiazole derivatives as potent acetylcholinesterase and butyrylcholinesterase enzyme inhibitors

Muhammad Taha
, Fazal Rahim
, Nizam Uddin
, Ihsan Ullah Khan
, Naveed Iqbal
, El Hassane Anouar
, Mohammed Salahuddin
, Rai Khalid Farooq
, Mohammed Gollapalli
, Khalid Mohammed Khan
, Ameeduzzafar Zafar

Chemistry

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1025-1036
Number of pages	12
Journal	International Journal of Biological Macromolecules
Volume	188
DOIs	https://doi.org/10.1016/j.ijbiomac.2021.08.065
State	Published - 1 Oct 2021

Keywords

Acetylcholinesterase
Butyrylcholinesterase
Indole-based-thiadiazole

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10.1016/j.ijbiomac.2021.08.065

Cite this

Taha, M., Rahim, F., Uddin, N., Khan, I. U., Iqbal, N., Anouar, E. H., Salahuddin, M., Farooq, R. K., Gollapalli, M., Khan, K. M., & Zafar, A. (2021). Exploring indole-based-thiadiazole derivatives as potent acetylcholinesterase and butyrylcholinesterase enzyme inhibitors. International Journal of Biological Macromolecules, 188, 1025-1036. https://doi.org/10.1016/j.ijbiomac.2021.08.065

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title = "Exploring indole-based-thiadiazole derivatives as potent acetylcholinesterase and butyrylcholinesterase enzyme inhibitors",

abstract = "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.",

keywords = "Acetylcholinesterase, Butyrylcholinesterase, Indole-based-thiadiazole",

author = "Muhammad Taha and Fazal Rahim and Nizam Uddin and Khan, \{Ihsan Ullah\} and Naveed Iqbal and Anouar, \{El Hassane\} and Mohammed Salahuddin and Farooq, \{Rai Khalid\} and Mohammed Gollapalli and Khan, \{Khalid Mohammed\} and Ameeduzzafar Zafar",

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year = "2021",

month = oct,

day = "1",

doi = "10.1016/j.ijbiomac.2021.08.065",

language = "English",

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Taha, M, Rahim, F, Uddin, N, Khan, IU, Iqbal, N, Anouar, EH, Salahuddin, M, Farooq, RK, Gollapalli, M, Khan, KM & Zafar, A 2021, 'Exploring indole-based-thiadiazole derivatives as potent acetylcholinesterase and butyrylcholinesterase enzyme inhibitors', International Journal of Biological Macromolecules, vol. 188, pp. 1025-1036. https://doi.org/10.1016/j.ijbiomac.2021.08.065

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

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 - https://www.scopus.com/pages/publications/85114818889

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 -

Exploring indole-based-thiadiazole derivatives as potent acetylcholinesterase and butyrylcholinesterase enzyme inhibitors

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Keywords

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