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Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity

[Image: see text] The aim of this work was to bring forth some new hybrid molecules having pharmacologically potent indole and 1,3,4-oxadiazole heterocyclic moieties unified with a propanamide entity. The synthetic methodology was initiated by esterification of 2-(1H-indol-3-yl)acetic acid (1) in a...

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Autores principales: Abbasi, Muhammad Athar, Rubab, Kaniz, Aziz-ur-Rehman, Siddiqui, Sabahat Zahra, Hassan, Mubashir, Raza, Hussain, Shah, Syed Adnan Ali, Shahid, Muhammad, Kloczkowski, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312992/
https://www.ncbi.nlm.nih.gov/pubmed/37396264
http://dx.doi.org/10.1021/acsomega.3c01882
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author Abbasi, Muhammad Athar
Rubab, Kaniz
Aziz-ur-Rehman
Siddiqui, Sabahat Zahra
Hassan, Mubashir
Raza, Hussain
Shah, Syed Adnan Ali
Shahid, Muhammad
Kloczkowski, Andrzej
author_facet Abbasi, Muhammad Athar
Rubab, Kaniz
Aziz-ur-Rehman
Siddiqui, Sabahat Zahra
Hassan, Mubashir
Raza, Hussain
Shah, Syed Adnan Ali
Shahid, Muhammad
Kloczkowski, Andrzej
author_sort Abbasi, Muhammad Athar
collection PubMed
description [Image: see text] The aim of this work was to bring forth some new hybrid molecules having pharmacologically potent indole and 1,3,4-oxadiazole heterocyclic moieties unified with a propanamide entity. The synthetic methodology was initiated by esterification of 2-(1H-indol-3-yl)acetic acid (1) in a catalytic amount of sulfuric acid and ethanol in excess, to form ethyl 2-(1H-indol-3-yl)acetate (2), which was converted to 2-(1H-indol-3-yl)acetohydrazide (3) and further transformed to 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). 3-Bromopropanoyl chloride (5) was reacted with various amines (6a–s) in aqueous alkaline medium to generate a series of electrophiles, 3-bromo-N-(substituted)propanamides (7a–s), and these were further reacted with nucleophile 4 in DMF and NaH base to yield the targeted N-(substituted)-3-{(5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl)sulfanyl}propanamides (8a–s). The chemical structures of these biheterocyclic propanamides were confirmed by IR, (1)H NMR, (13)C NMR, and EI-MS spectral techniques. These compounds were evaluated for their enzyme inhibitory potentials against the α-glucosidase enzyme, where the compound 8l showed promising enzyme inhibitory potential with an IC(50) value less than that of the standard acarbose. Molecular docking results of these molecules were coherent with the results of their enzyme inhibitory potentials. Cytotoxicity was assessed by the percentage of hemolytic activity method, and these compounds generally exhibited very low values as compared to the reference standard, Triton-X. Hence, some of these biheterocyclic propanamides might be considered as salient therapeutic agents in further stages of antidiabetic drug development.
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spelling pubmed-103129922023-07-01 Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity Abbasi, Muhammad Athar Rubab, Kaniz Aziz-ur-Rehman Siddiqui, Sabahat Zahra Hassan, Mubashir Raza, Hussain Shah, Syed Adnan Ali Shahid, Muhammad Kloczkowski, Andrzej ACS Omega [Image: see text] The aim of this work was to bring forth some new hybrid molecules having pharmacologically potent indole and 1,3,4-oxadiazole heterocyclic moieties unified with a propanamide entity. The synthetic methodology was initiated by esterification of 2-(1H-indol-3-yl)acetic acid (1) in a catalytic amount of sulfuric acid and ethanol in excess, to form ethyl 2-(1H-indol-3-yl)acetate (2), which was converted to 2-(1H-indol-3-yl)acetohydrazide (3) and further transformed to 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). 3-Bromopropanoyl chloride (5) was reacted with various amines (6a–s) in aqueous alkaline medium to generate a series of electrophiles, 3-bromo-N-(substituted)propanamides (7a–s), and these were further reacted with nucleophile 4 in DMF and NaH base to yield the targeted N-(substituted)-3-{(5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl)sulfanyl}propanamides (8a–s). The chemical structures of these biheterocyclic propanamides were confirmed by IR, (1)H NMR, (13)C NMR, and EI-MS spectral techniques. These compounds were evaluated for their enzyme inhibitory potentials against the α-glucosidase enzyme, where the compound 8l showed promising enzyme inhibitory potential with an IC(50) value less than that of the standard acarbose. Molecular docking results of these molecules were coherent with the results of their enzyme inhibitory potentials. Cytotoxicity was assessed by the percentage of hemolytic activity method, and these compounds generally exhibited very low values as compared to the reference standard, Triton-X. Hence, some of these biheterocyclic propanamides might be considered as salient therapeutic agents in further stages of antidiabetic drug development. American Chemical Society 2023-06-14 /pmc/articles/PMC10312992/ /pubmed/37396264 http://dx.doi.org/10.1021/acsomega.3c01882 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Abbasi, Muhammad Athar
Rubab, Kaniz
Aziz-ur-Rehman
Siddiqui, Sabahat Zahra
Hassan, Mubashir
Raza, Hussain
Shah, Syed Adnan Ali
Shahid, Muhammad
Kloczkowski, Andrzej
Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity
title Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity
title_full Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity
title_fullStr Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity
title_full_unstemmed Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity
title_short Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity
title_sort synthesis and molecular docking studies of novel biheterocyclic propanamides as antidiabetic agents having mild cytotoxicity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312992/
https://www.ncbi.nlm.nih.gov/pubmed/37396264
http://dx.doi.org/10.1021/acsomega.3c01882
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