Cargando…
Bio-Oriented Synthesis of Novel Polyhydroquinoline Derivatives as α-Glucosidase Inhibitor for Management of Diabetes
[Image: see text] Polyhydroquinoline derivatives (1-15) were synthesized through an unsymmetrical Hantzsch reaction in excellent yields by treating 3,5-dibromo-4-hydroxybenzaldehyde, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol solvent. The structures of the synthesized compounds (1...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9948207/ https://www.ncbi.nlm.nih.gov/pubmed/36844517 http://dx.doi.org/10.1021/acsomega.2c05390 |
_version_ | 1784892729343344640 |
---|---|
author | Talab, Faiz Ullah, Saeed Alam, Aftab Halim, Sobia Ahsan Rehman, Najeeb Ur Zainab, Ali, Mumtaz Latif, Abdul Khan, Ajmal Al-Harrasi, Ahmed Ahmad, Manzoor |
author_facet | Talab, Faiz Ullah, Saeed Alam, Aftab Halim, Sobia Ahsan Rehman, Najeeb Ur Zainab, Ali, Mumtaz Latif, Abdul Khan, Ajmal Al-Harrasi, Ahmed Ahmad, Manzoor |
author_sort | Talab, Faiz |
collection | PubMed |
description | [Image: see text] Polyhydroquinoline derivatives (1-15) were synthesized through an unsymmetrical Hantzsch reaction in excellent yields by treating 3,5-dibromo-4-hydroxybenzaldehyde, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol solvent. The structures of the synthesized compounds (1-15) were deduced through different spectroscopic techniques such as (1)H NMR, (13)C NMR, and HR–ESI–MS. The synthesized products were tested for their α-glucosidase inhibitory activity where compounds 11 (IC(50)= 0.56 ± 0.01 μM), 10 (IC(50)= 0.94 ± 0.01 μM), 4 (IC(50)= 1.47 ± 0.01 μM), 2 (IC(50)= 2.20 ± 0.03 μM), 6 (IC(50)= 2.20 ± 0.03 μM), 12 (IC(50)= 2.22 ± 0.07 μM), 7 (IC(50)= 2.76 ± 0.04 μM), 9 (IC(50)= 2.78 ± 0.03 μM), and 3 (IC(50)= 2.88 ± 0.05 μM) exhibited high potential for the inhibition of α-glucosidase, while the rest of the compounds (8, 5, 14, 15, and 13) showed significant α-glucosidase inhibitory potential with IC(50) values of 3.13 ± 0.10, 3.34 ± 0.06, 4.27 ± 0.13, 6.34 ± 0.15, and 21.37 ± 0.61 μM, respectively. Among the synthesized series, two compounds, i.e., 11 and 10, showed potent α-glucosidase inhibitory potential higher than the standard. All the compounds were compared with standard drug “acarbose” (IC(50) = 873.34 ± 1.67 μM). An in silico method was used to predict their mode of binding within the active site of enzyme to understand their mechanism of inhibition. Our in silico observation complements with the experimental results. |
format | Online Article Text |
id | pubmed-9948207 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-99482072023-02-24 Bio-Oriented Synthesis of Novel Polyhydroquinoline Derivatives as α-Glucosidase Inhibitor for Management of Diabetes Talab, Faiz Ullah, Saeed Alam, Aftab Halim, Sobia Ahsan Rehman, Najeeb Ur Zainab, Ali, Mumtaz Latif, Abdul Khan, Ajmal Al-Harrasi, Ahmed Ahmad, Manzoor ACS Omega [Image: see text] Polyhydroquinoline derivatives (1-15) were synthesized through an unsymmetrical Hantzsch reaction in excellent yields by treating 3,5-dibromo-4-hydroxybenzaldehyde, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol solvent. The structures of the synthesized compounds (1-15) were deduced through different spectroscopic techniques such as (1)H NMR, (13)C NMR, and HR–ESI–MS. The synthesized products were tested for their α-glucosidase inhibitory activity where compounds 11 (IC(50)= 0.56 ± 0.01 μM), 10 (IC(50)= 0.94 ± 0.01 μM), 4 (IC(50)= 1.47 ± 0.01 μM), 2 (IC(50)= 2.20 ± 0.03 μM), 6 (IC(50)= 2.20 ± 0.03 μM), 12 (IC(50)= 2.22 ± 0.07 μM), 7 (IC(50)= 2.76 ± 0.04 μM), 9 (IC(50)= 2.78 ± 0.03 μM), and 3 (IC(50)= 2.88 ± 0.05 μM) exhibited high potential for the inhibition of α-glucosidase, while the rest of the compounds (8, 5, 14, 15, and 13) showed significant α-glucosidase inhibitory potential with IC(50) values of 3.13 ± 0.10, 3.34 ± 0.06, 4.27 ± 0.13, 6.34 ± 0.15, and 21.37 ± 0.61 μM, respectively. Among the synthesized series, two compounds, i.e., 11 and 10, showed potent α-glucosidase inhibitory potential higher than the standard. All the compounds were compared with standard drug “acarbose” (IC(50) = 873.34 ± 1.67 μM). An in silico method was used to predict their mode of binding within the active site of enzyme to understand their mechanism of inhibition. Our in silico observation complements with the experimental results. American Chemical Society 2023-02-08 /pmc/articles/PMC9948207/ /pubmed/36844517 http://dx.doi.org/10.1021/acsomega.2c05390 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 | Talab, Faiz Ullah, Saeed Alam, Aftab Halim, Sobia Ahsan Rehman, Najeeb Ur Zainab, Ali, Mumtaz Latif, Abdul Khan, Ajmal Al-Harrasi, Ahmed Ahmad, Manzoor Bio-Oriented Synthesis of Novel Polyhydroquinoline Derivatives as α-Glucosidase Inhibitor for Management of Diabetes |
title | Bio-Oriented Synthesis of Novel Polyhydroquinoline
Derivatives as α-Glucosidase Inhibitor for Management
of Diabetes |
title_full | Bio-Oriented Synthesis of Novel Polyhydroquinoline
Derivatives as α-Glucosidase Inhibitor for Management
of Diabetes |
title_fullStr | Bio-Oriented Synthesis of Novel Polyhydroquinoline
Derivatives as α-Glucosidase Inhibitor for Management
of Diabetes |
title_full_unstemmed | Bio-Oriented Synthesis of Novel Polyhydroquinoline
Derivatives as α-Glucosidase Inhibitor for Management
of Diabetes |
title_short | Bio-Oriented Synthesis of Novel Polyhydroquinoline
Derivatives as α-Glucosidase Inhibitor for Management
of Diabetes |
title_sort | bio-oriented synthesis of novel polyhydroquinoline
derivatives as α-glucosidase inhibitor for management
of diabetes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9948207/ https://www.ncbi.nlm.nih.gov/pubmed/36844517 http://dx.doi.org/10.1021/acsomega.2c05390 |
work_keys_str_mv | AT talabfaiz bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT ullahsaeed bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT alamaftab bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT halimsobiaahsan bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT rehmannajeebur bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT zainab bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT alimumtaz bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT latifabdul bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT khanajmal bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT alharrasiahmed bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes AT ahmadmanzoor bioorientedsynthesisofnovelpolyhydroquinolinederivativesasaglucosidaseinhibitorformanagementofdiabetes |