2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies

In this study, we aimed to (i) synthesize new 2-methylindole analogs containing various amino structures, pyrrolidine, piperidine, morpholine, and substituted phenyl groups through structural and molecular modifications, (ii) evaluate the pharmaceutical potential of 2-methylindole analogs via assess...

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Autores principales:	Adnan Cetin, Ercan Bursal, Fikret Türkan
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Acetylcholinesterase Computational studies Drug design Enzyme inhibition Molecular docking Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/fad31ebb36c449be87eb404884a6152b
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spelling	oai:doaj.org-article:fad31ebb36c449be87eb404884a6152b2021-11-20T04:58:09Z2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies1878-535210.1016/j.arabjc.2021.103449https://doaj.org/article/fad31ebb36c449be87eb404884a6152b2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1878535221004640https://doaj.org/toc/1878-5352In this study, we aimed to (i) synthesize new 2-methylindole analogs containing various amino structures, pyrrolidine, piperidine, morpholine, and substituted phenyl groups through structural and molecular modifications, (ii) evaluate the pharmaceutical potential of 2-methylindole analogs via assessing enzyme inhibitory activity against glutathione S-transferase (GST), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), (iii) predict ADMET and pharmacokinetic properties of the synthesized 2-methylindole analogs, (iv) reveal the possible interactions between the synthesized 2-methylindole analogs with GST, AChE, and BChE enzymes using several molecular docking software. In vitro enzyme inhibition assays showed that the synthesized indole analogs exhibited moderate to good inhibitory activities against GST, AChE, and BChE enzymes. Briefly, the inhibitory activities of the analogs 4b and 4i against AChE, 4a and 4b against BChE, and analogs 1 and 4i against GST were detected to be higher or close to the standard inhibitor compounds. The analog 4b was detected to have the best inhibitory activity against both AChE and BChE enzymes with the lowest IC50 values as 0.648 µM for AChE and 0.745 µM for BChE. The analyses of enzyme inhibition relationship with the synthesized analogs could help to design new analogs for the inhibitors of cholinergic and glutathione pathways based on the indole derivatives.Adnan CetinErcan BursalFikret TürkanElsevierarticleAcetylcholinesteraseComputational studiesDrug designEnzyme inhibitionMolecular dockingChemistryQD1-999ENArabian Journal of Chemistry, Vol 14, Iss 12, Pp 103449- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acetylcholinesterase Computational studies Drug design Enzyme inhibition Molecular docking Chemistry QD1-999
spellingShingle	Acetylcholinesterase Computational studies Drug design Enzyme inhibition Molecular docking Chemistry QD1-999 Adnan Cetin Ercan Bursal Fikret Türkan 2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies
description	In this study, we aimed to (i) synthesize new 2-methylindole analogs containing various amino structures, pyrrolidine, piperidine, morpholine, and substituted phenyl groups through structural and molecular modifications, (ii) evaluate the pharmaceutical potential of 2-methylindole analogs via assessing enzyme inhibitory activity against glutathione S-transferase (GST), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), (iii) predict ADMET and pharmacokinetic properties of the synthesized 2-methylindole analogs, (iv) reveal the possible interactions between the synthesized 2-methylindole analogs with GST, AChE, and BChE enzymes using several molecular docking software. In vitro enzyme inhibition assays showed that the synthesized indole analogs exhibited moderate to good inhibitory activities against GST, AChE, and BChE enzymes. Briefly, the inhibitory activities of the analogs 4b and 4i against AChE, 4a and 4b against BChE, and analogs 1 and 4i against GST were detected to be higher or close to the standard inhibitor compounds. The analog 4b was detected to have the best inhibitory activity against both AChE and BChE enzymes with the lowest IC50 values as 0.648 µM for AChE and 0.745 µM for BChE. The analyses of enzyme inhibition relationship with the synthesized analogs could help to design new analogs for the inhibitors of cholinergic and glutathione pathways based on the indole derivatives.
format	article
author	Adnan Cetin Ercan Bursal Fikret Türkan
author_facet	Adnan Cetin Ercan Bursal Fikret Türkan
author_sort	Adnan Cetin
title	2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies
title_short	2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies
title_full	2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies
title_fullStr	2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies
title_full_unstemmed	2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies
title_sort	2-methylindole analogs as cholinesterases and glutathione s-transferase inhibitors: synthesis, biological evaluation, molecular docking, and pharmacokinetic studies
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/fad31ebb36c449be87eb404884a6152b
work_keys_str_mv	AT adnancetin 2methylindoleanalogsascholinesterasesandglutathionestransferaseinhibitorssynthesisbiologicalevaluationmoleculardockingandpharmacokineticstudies AT ercanbursal 2methylindoleanalogsascholinesterasesandglutathionestransferaseinhibitorssynthesisbiologicalevaluationmoleculardockingandpharmacokineticstudies AT fikretturkan 2methylindoleanalogsascholinesterasesandglutathionestransferaseinhibitorssynthesisbiologicalevaluationmoleculardockingandpharmacokineticstudies
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2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies

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