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Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors
Here, we report the synthesis, carbonic anhydrase-II (CA-II) inhibition and structure–activity relationship studies of cinnamaldehyde-clubbed thiosemicarbazones derivatives. The derivatives showed potent activities in the range of 10.3 ± 0.62–46.6 ± 0.62 µM. Among all the synthesized derivatives, co...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515202/ https://www.ncbi.nlm.nih.gov/pubmed/36167735 http://dx.doi.org/10.1038/s41598-022-19975-y |
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author | Rasool, Asif Batool, Zahra Khan, Majid Halim, Sobia Ahsan Shafiq, Zahid Temirak, Ahmed Salem, Mohamed A. Ali, Tarik E. Khan, Ajmal Al-Harrasi, Ahmed |
author_facet | Rasool, Asif Batool, Zahra Khan, Majid Halim, Sobia Ahsan Shafiq, Zahid Temirak, Ahmed Salem, Mohamed A. Ali, Tarik E. Khan, Ajmal Al-Harrasi, Ahmed |
author_sort | Rasool, Asif |
collection | PubMed |
description | Here, we report the synthesis, carbonic anhydrase-II (CA-II) inhibition and structure–activity relationship studies of cinnamaldehyde-clubbed thiosemicarbazones derivatives. The derivatives showed potent activities in the range of 10.3 ± 0.62–46.6 ± 0.62 µM. Among all the synthesized derivatives, compound 3n (IC(50) = 10.3 ± 0.62 µM), 3g (IC(50) = 12.1 ± 1.01 µM), and 3h (IC(50) = 13.4 ± 0.52 µM) showed higher inhibitory activity as compared to the standard inhibitor, acetazolamide. Furthermore, molecular docking of all the active compounds was carried out to predict their behavior of molecular binding. The docking results indicate that the most active hit (3n) specifically mediate ionic interaction with the Zn ion in the active site of CA-II. Furthermore, the The199 and Thr200 support the binding of thiosemicarbazide moiety of 3n, while Gln 92 supports the interactions of all the compounds by hydrogen bonding. In addition to Gln92, few other residues including Asn62, Asn67, The199, and Thr200 play important role in the stabilization of these molecules in the active site by specifically providing H-bonds to the thiosemicarbazide moiety of compounds. The docking score of active hits are found in range of − 6.75 to − 4.42 kcal/mol, which indicates that the computational prediction correlates well with the in vitro results. |
format | Online Article Text |
id | pubmed-9515202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95152022022-09-29 Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors Rasool, Asif Batool, Zahra Khan, Majid Halim, Sobia Ahsan Shafiq, Zahid Temirak, Ahmed Salem, Mohamed A. Ali, Tarik E. Khan, Ajmal Al-Harrasi, Ahmed Sci Rep Article Here, we report the synthesis, carbonic anhydrase-II (CA-II) inhibition and structure–activity relationship studies of cinnamaldehyde-clubbed thiosemicarbazones derivatives. The derivatives showed potent activities in the range of 10.3 ± 0.62–46.6 ± 0.62 µM. Among all the synthesized derivatives, compound 3n (IC(50) = 10.3 ± 0.62 µM), 3g (IC(50) = 12.1 ± 1.01 µM), and 3h (IC(50) = 13.4 ± 0.52 µM) showed higher inhibitory activity as compared to the standard inhibitor, acetazolamide. Furthermore, molecular docking of all the active compounds was carried out to predict their behavior of molecular binding. The docking results indicate that the most active hit (3n) specifically mediate ionic interaction with the Zn ion in the active site of CA-II. Furthermore, the The199 and Thr200 support the binding of thiosemicarbazide moiety of 3n, while Gln 92 supports the interactions of all the compounds by hydrogen bonding. In addition to Gln92, few other residues including Asn62, Asn67, The199, and Thr200 play important role in the stabilization of these molecules in the active site by specifically providing H-bonds to the thiosemicarbazide moiety of compounds. The docking score of active hits are found in range of − 6.75 to − 4.42 kcal/mol, which indicates that the computational prediction correlates well with the in vitro results. Nature Publishing Group UK 2022-09-27 /pmc/articles/PMC9515202/ /pubmed/36167735 http://dx.doi.org/10.1038/s41598-022-19975-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Rasool, Asif Batool, Zahra Khan, Majid Halim, Sobia Ahsan Shafiq, Zahid Temirak, Ahmed Salem, Mohamed A. Ali, Tarik E. Khan, Ajmal Al-Harrasi, Ahmed Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors |
title | Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors |
title_full | Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors |
title_fullStr | Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors |
title_full_unstemmed | Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors |
title_short | Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors |
title_sort | bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-ii inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515202/ https://www.ncbi.nlm.nih.gov/pubmed/36167735 http://dx.doi.org/10.1038/s41598-022-19975-y |
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