Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of N-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against Helicobacter pylori

Gastrointestinal tract infection caused by Helicobacter pylori is a common virulent disease found worldwide, and the infection rate is much higher in developing countries than in developed ones. In the pathogenesis of H. pylori in the gastrointestinal tract, the...

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Autores principales:	Ishani P. Kalatuwawege, Medha J. Gunaratna, Dinusha N. Udukala
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Helicobacter pylori</i> urease inhibitors indole-3-carbaldehyde oximes isomerization molecular docking Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/e99bf2e07c804c20ae6cff5cc68123ce
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spelling	oai:doaj.org-article:e99bf2e07c804c20ae6cff5cc68123ce2021-11-11T18:37:24ZSynthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of <i>N</i>-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against <i>Helicobacter pylori</i>10.3390/molecules262166581420-3049https://doaj.org/article/e99bf2e07c804c20ae6cff5cc68123ce2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6658https://doaj.org/toc/1420-3049Gastrointestinal tract infection caused by <i>Helicobacter pylori</i> is a common virulent disease found worldwide, and the infection rate is much higher in developing countries than in developed ones. In the pathogenesis of <i>H. pylori</i> in the gastrointestinal tract, the secretion of the urease enzyme plays a major role. Therefore, inhibition of urease is a better approach against <i>H. pylori</i> infection. In the present study, a series of syn and anti isomers of <i>N</i>-substituted indole-3-carbaldehyde oxime derivatives was synthesized via Schiff base reaction of appropriate carbaldehyde derivatives with hydroxylamine hydrochloride. The in vitro urease inhibitory activities of those derivatives were evaluated against that of <i>Macrotyloma uniflorum</i> urease using the modified Berthelot reaction. Out of the tested compounds, compound <b>8</b> (IC<sub>50</sub> = 0.0516 ± 0.0035 mM) and compound <b>9</b> (IC<sub>50</sub> = 0.0345 ± 0.0008 mM) were identified as the derivatives with potent urease inhibitory activity with compared to thiourea (IC<sub>50</sub> = 0.2387 ± 0.0048 mM). Additionally, in silico studies for all oxime compounds were performed to investigate the binding interactions with the active site of the urease enzyme compared to thiourea. Furthermore, the drug-likeness of the synthesized oxime compounds was also predicted.Ishani P. KalatuwawegeMedha J. GunaratnaDinusha N. UdukalaMDPI AGarticle<i>Helicobacter pylori</i>urease inhibitorsindole-3-carbaldehyde oximesisomerizationmolecular dockingOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6658, p 6658 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Helicobacter pylori</i> urease inhibitors indole-3-carbaldehyde oximes isomerization molecular docking Organic chemistry QD241-441
spellingShingle	<i>Helicobacter pylori</i> urease inhibitors indole-3-carbaldehyde oximes isomerization molecular docking Organic chemistry QD241-441 Ishani P. Kalatuwawege Medha J. Gunaratna Dinusha N. Udukala Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of <i>N</i>-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against <i>Helicobacter pylori</i>
description	Gastrointestinal tract infection caused by <i>Helicobacter pylori</i> is a common virulent disease found worldwide, and the infection rate is much higher in developing countries than in developed ones. In the pathogenesis of <i>H. pylori</i> in the gastrointestinal tract, the secretion of the urease enzyme plays a major role. Therefore, inhibition of urease is a better approach against <i>H. pylori</i> infection. In the present study, a series of syn and anti isomers of <i>N</i>-substituted indole-3-carbaldehyde oxime derivatives was synthesized via Schiff base reaction of appropriate carbaldehyde derivatives with hydroxylamine hydrochloride. The in vitro urease inhibitory activities of those derivatives were evaluated against that of <i>Macrotyloma uniflorum</i> urease using the modified Berthelot reaction. Out of the tested compounds, compound <b>8</b> (IC<sub>50</sub> = 0.0516 ± 0.0035 mM) and compound <b>9</b> (IC<sub>50</sub> = 0.0345 ± 0.0008 mM) were identified as the derivatives with potent urease inhibitory activity with compared to thiourea (IC<sub>50</sub> = 0.2387 ± 0.0048 mM). Additionally, in silico studies for all oxime compounds were performed to investigate the binding interactions with the active site of the urease enzyme compared to thiourea. Furthermore, the drug-likeness of the synthesized oxime compounds was also predicted.
format	article
author	Ishani P. Kalatuwawege Medha J. Gunaratna Dinusha N. Udukala
author_facet	Ishani P. Kalatuwawege Medha J. Gunaratna Dinusha N. Udukala
author_sort	Ishani P. Kalatuwawege
title	Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of <i>N</i>-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against <i>Helicobacter pylori</i>
title_short	Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of <i>N</i>-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against <i>Helicobacter pylori</i>
title_full	Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of <i>N</i>-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against <i>Helicobacter pylori</i>
title_fullStr	Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of <i>N</i>-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against <i>Helicobacter pylori</i>
title_full_unstemmed	Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of <i>N</i>-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against <i>Helicobacter pylori</i>
title_sort	synthesis, in silico studies, and evaluation of syn and anti isomers of <i>n</i>-substituted indole-3-carbaldehyde oxime derivatives as urease inhibitors against <i>helicobacter pylori</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e99bf2e07c804c20ae6cff5cc68123ce
work_keys_str_mv	AT ishanipkalatuwawege synthesisinsilicostudiesandevaluationofsynandantiisomersofinisubstitutedindole3carbaldehydeoximederivativesasureaseinhibitorsagainstihelicobacterpylorii AT medhajgunaratna synthesisinsilicostudiesandevaluationofsynandantiisomersofinisubstitutedindole3carbaldehydeoximederivativesasureaseinhibitorsagainstihelicobacterpylorii AT dinushanudukala synthesisinsilicostudiesandevaluationofsynandantiisomersofinisubstitutedindole3carbaldehydeoximederivativesasureaseinhibitorsagainstihelicobacterpylorii
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Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of <i>N</i>-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against <i>Helicobacter pylori</i>

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