Synthesis, Biological Evaluation, and In Silico Studies of Novel Coumarin-Based 4 H ,5 H -pyrano[3,2- c ]chromenes as Potent β-Glucuronidase and Carbonic Anhydrase Inhibitors.

Autor: Arif N; Institute of Chemical Sciences, Organic Chemistry Division, Bahauddin Zakariya University, Multan 60800, Pakistan., Shafiq Z; Institute of Chemical Sciences, Organic Chemistry Division, Bahauddin Zakariya University, Multan 60800, Pakistan.; Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany., Mahmood K; Institute of Chemical Sciences, Organic Chemistry Division, Bahauddin Zakariya University, Multan 60800, Pakistan., Rafiq M; Institute of Chemical Sciences, Organic Chemistry Division, Bahauddin Zakariya University, Multan 60800, Pakistan., Naz S; Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan., Shahzad SA; Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan., Farooq U; Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan., Bahkali AH; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia., Elgorban AM; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia., Yaqub M; Institute of Chemical Sciences, Organic Chemistry Division, Bahauddin Zakariya University, Multan 60800, Pakistan., El-Gokha A; Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.; Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2022 Aug 04; Vol. 7 (32), pp. 28605-28617. Date of Electronic Publication: 2022 Aug 04 (Print Publication: 2022).
DOI: 10.1021/acsomega.2c03528
Abstrakt: 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.
Competing Interests: The authors declare no competing financial interest.
(© 2022 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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