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Synthesis, Biological Evaluation, and In Silico Studies of Novel Coumarin-Based 4H,5H-pyrano[3,2-c]chromenes as Potent β-Glucuronidase and Carbonic Anhydrase Inhibitors
[Image: see text] The search for novel heterocyclic compounds with a natural product skeleton as potent enzyme inhibitors against clinical hits is our prime concern in this study. Here, a simple and facile two-step strategy has been designed to synthesize a series of novel coumarin-based dihydropyra...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386806/ https://www.ncbi.nlm.nih.gov/pubmed/35990487 http://dx.doi.org/10.1021/acsomega.2c03528 |
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author | Arif, Nadia Shafiq, Zahid Mahmood, Khalid Rafiq, Muhammad Naz, Sadia Shahzad, Sohail Anjum Farooq, Umar Bahkali, Ali H. Elgorban, Abdallah M. Yaqub, Muhammad El-Gokha, Ahmed |
author_facet | Arif, Nadia Shafiq, Zahid Mahmood, Khalid Rafiq, Muhammad Naz, Sadia Shahzad, Sohail Anjum Farooq, Umar Bahkali, Ali H. Elgorban, Abdallah M. Yaqub, Muhammad El-Gokha, Ahmed |
author_sort | Arif, Nadia |
collection | PubMed |
description | [Image: see text] The search for novel heterocyclic compounds with a natural product skeleton as potent enzyme inhibitors against clinical hits is our prime concern in this study. Here, a simple and facile two-step strategy has been designed to synthesize a series of novel coumarin-based dihydropyranochromenes (12a–12m) in a basic moiety. The synthesized compounds were thus characterized through spectroscopic techniques and screened for inhibition potency against the cytosolic hCA II isoform and β-glucuronidase. Few of these compounds were potent inhibitors of hCA II and β-glucuronidase with varying IC(50) values ranging from 4.55 ± 0.22 to 21.77 ± 3.32 μM and 440.1 ± 1.17 to 971.3 ± 0.05 μM, respectively. Among the stream of synthesized compounds, 12e and 12i were the most potent inhibitors of β-glucuronidase, while 12h, 12i, and 12j showed greater potency against hCA II. In silico docking studies illustrated the significance of substituted groups on the pyranochromene skeleton and binding pattern of these highly potent compounds inside enzyme pockets. |
format | Online Article Text |
id | pubmed-9386806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-93868062022-08-19 Synthesis, Biological Evaluation, and In Silico Studies of Novel Coumarin-Based 4H,5H-pyrano[3,2-c]chromenes as Potent β-Glucuronidase and Carbonic Anhydrase Inhibitors Arif, Nadia Shafiq, Zahid Mahmood, Khalid Rafiq, Muhammad Naz, Sadia Shahzad, Sohail Anjum Farooq, Umar Bahkali, Ali H. Elgorban, Abdallah M. Yaqub, Muhammad El-Gokha, Ahmed ACS Omega [Image: see text] The search for novel heterocyclic compounds with a natural product skeleton as potent enzyme inhibitors against clinical hits is our prime concern in this study. Here, a simple and facile two-step strategy has been designed to synthesize a series of novel coumarin-based dihydropyranochromenes (12a–12m) in a basic moiety. The synthesized compounds were thus characterized through spectroscopic techniques and screened for inhibition potency against the cytosolic hCA II isoform and β-glucuronidase. Few of these compounds were potent inhibitors of hCA II and β-glucuronidase with varying IC(50) values ranging from 4.55 ± 0.22 to 21.77 ± 3.32 μM and 440.1 ± 1.17 to 971.3 ± 0.05 μM, respectively. Among the stream of synthesized compounds, 12e and 12i were the most potent inhibitors of β-glucuronidase, while 12h, 12i, and 12j showed greater potency against hCA II. In silico docking studies illustrated the significance of substituted groups on the pyranochromene skeleton and binding pattern of these highly potent compounds inside enzyme pockets. American Chemical Society 2022-08-04 /pmc/articles/PMC9386806/ /pubmed/35990487 http://dx.doi.org/10.1021/acsomega.2c03528 Text en © 2022 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 | Arif, Nadia Shafiq, Zahid Mahmood, Khalid Rafiq, Muhammad Naz, Sadia Shahzad, Sohail Anjum Farooq, Umar Bahkali, Ali H. Elgorban, Abdallah M. Yaqub, Muhammad El-Gokha, Ahmed Synthesis, Biological Evaluation, and In Silico Studies of Novel Coumarin-Based 4H,5H-pyrano[3,2-c]chromenes as Potent β-Glucuronidase and Carbonic Anhydrase Inhibitors |
title | Synthesis, Biological
Evaluation, and In Silico Studies of Novel Coumarin-Based
4H,5H-pyrano[3,2-c]chromenes as Potent
β-Glucuronidase and Carbonic Anhydrase Inhibitors |
title_full | Synthesis, Biological
Evaluation, and In Silico Studies of Novel Coumarin-Based
4H,5H-pyrano[3,2-c]chromenes as Potent
β-Glucuronidase and Carbonic Anhydrase Inhibitors |
title_fullStr | Synthesis, Biological
Evaluation, and In Silico Studies of Novel Coumarin-Based
4H,5H-pyrano[3,2-c]chromenes as Potent
β-Glucuronidase and Carbonic Anhydrase Inhibitors |
title_full_unstemmed | Synthesis, Biological
Evaluation, and In Silico Studies of Novel Coumarin-Based
4H,5H-pyrano[3,2-c]chromenes as Potent
β-Glucuronidase and Carbonic Anhydrase Inhibitors |
title_short | Synthesis, Biological
Evaluation, and In Silico Studies of Novel Coumarin-Based
4H,5H-pyrano[3,2-c]chromenes as Potent
β-Glucuronidase and Carbonic Anhydrase Inhibitors |
title_sort | synthesis, biological
evaluation, and in silico studies of novel coumarin-based
4h,5h-pyrano[3,2-c]chromenes as potent
β-glucuronidase and carbonic anhydrase inhibitors |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386806/ https://www.ncbi.nlm.nih.gov/pubmed/35990487 http://dx.doi.org/10.1021/acsomega.2c03528 |
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