Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors

Diabetes is an emerging metabolic disorder. α-Glucosidase inhibitors, such as acarbose, delay the hydrolysis of carbohydrates by interfering with the digestive enzymes. This action decreases the glucose absorption and the postprandial glucose level. We have synthesized 25 tricyclic 2-phenoxypyrido[3...

Descripción completa

Detalles Bibliográficos
Autores principales: Abuelizz, Hatem A., Iwana, Nor Azman N. I., Ahmad, Rohaya, Anouar, El-Hassane, Marzouk, Mohamed, Al-Salahi, Rashad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661812/
https://www.ncbi.nlm.nih.gov/pubmed/31384800
http://dx.doi.org/10.1186/s13065-019-0560-4
_version_ 1783439532020989952
author Abuelizz, Hatem A.
Iwana, Nor Azman N. I.
Ahmad, Rohaya
Anouar, El-Hassane
Marzouk, Mohamed
Al-Salahi, Rashad
author_facet Abuelizz, Hatem A.
Iwana, Nor Azman N. I.
Ahmad, Rohaya
Anouar, El-Hassane
Marzouk, Mohamed
Al-Salahi, Rashad
author_sort Abuelizz, Hatem A.
collection PubMed
description Diabetes is an emerging metabolic disorder. α-Glucosidase inhibitors, such as acarbose, delay the hydrolysis of carbohydrates by interfering with the digestive enzymes. This action decreases the glucose absorption and the postprandial glucose level. We have synthesized 25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids and evaluated their α-glucosidase inhibitory activity. Compounds 6h and 6d have shown stronger activity than that of acarbose. Compound 6h exhibited the highest inhibition with an IC(50) of 104.07 µM. Molecular modelling studies revealed that compound 6h inhibits α-glucosidase due to the formation of a stable ligand-α-glucosidase complex and extra hydrogen bond interactions, and directed in the binding site by Trp329. [Figure: see text]
format Online
Article
Text
id pubmed-6661812
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Springer International Publishing
record_format MEDLINE/PubMed
spelling pubmed-66618122019-08-05 Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors Abuelizz, Hatem A. Iwana, Nor Azman N. I. Ahmad, Rohaya Anouar, El-Hassane Marzouk, Mohamed Al-Salahi, Rashad BMC Chem Research Article Diabetes is an emerging metabolic disorder. α-Glucosidase inhibitors, such as acarbose, delay the hydrolysis of carbohydrates by interfering with the digestive enzymes. This action decreases the glucose absorption and the postprandial glucose level. We have synthesized 25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids and evaluated their α-glucosidase inhibitory activity. Compounds 6h and 6d have shown stronger activity than that of acarbose. Compound 6h exhibited the highest inhibition with an IC(50) of 104.07 µM. Molecular modelling studies revealed that compound 6h inhibits α-glucosidase due to the formation of a stable ligand-α-glucosidase complex and extra hydrogen bond interactions, and directed in the binding site by Trp329. [Figure: see text] Springer International Publishing 2019-04-05 /pmc/articles/PMC6661812/ /pubmed/31384800 http://dx.doi.org/10.1186/s13065-019-0560-4 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Abuelizz, Hatem A.
Iwana, Nor Azman N. I.
Ahmad, Rohaya
Anouar, El-Hassane
Marzouk, Mohamed
Al-Salahi, Rashad
Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors
title Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors
title_full Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors
title_fullStr Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors
title_full_unstemmed Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors
title_short Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors
title_sort synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661812/
https://www.ncbi.nlm.nih.gov/pubmed/31384800
http://dx.doi.org/10.1186/s13065-019-0560-4
work_keys_str_mv AT abuelizzhatema synthesisbiologicalactivityandmoleculardockingofnewtricyclicseriesasaglucosidaseinhibitors
AT iwananorazmanni synthesisbiologicalactivityandmoleculardockingofnewtricyclicseriesasaglucosidaseinhibitors
AT ahmadrohaya synthesisbiologicalactivityandmoleculardockingofnewtricyclicseriesasaglucosidaseinhibitors
AT anouarelhassane synthesisbiologicalactivityandmoleculardockingofnewtricyclicseriesasaglucosidaseinhibitors
AT marzoukmohamed synthesisbiologicalactivityandmoleculardockingofnewtricyclicseriesasaglucosidaseinhibitors
AT alsalahirashad synthesisbiologicalactivityandmoleculardockingofnewtricyclicseriesasaglucosidaseinhibitors

Ejemplares similares