Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors
Abstract 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 deriva...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-19975-y |
| _version_ | 1811200906809573376 |
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| author | Asif Rasool Zahra Batool Majid Khan Sobia Ahsan Halim Zahid Shafiq Ahmed Temirak Mohamed A. Salem Tarik E. Ali Ajmal Khan Ahmed Al-Harrasi |
| author_facet | Asif Rasool Zahra Batool Majid Khan Sobia Ahsan Halim Zahid Shafiq Ahmed Temirak Mohamed A. Salem Tarik E. Ali Ajmal Khan Ahmed Al-Harrasi |
| author_sort | Asif Rasool |
| collection | DOAJ |
| description | Abstract 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 (IC50 = 10.3 ± 0.62 µM), 3g (IC50 = 12.1 ± 1.01 µM), and 3h (IC50 = 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. |
| first_indexed | 2024-04-12T02:11:40Z |
| format | Article |
| id | doaj.art-b4aea743ed0d42d8be3f497412acf058 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T02:11:40Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b4aea743ed0d42d8be3f497412acf0582022-12-22T03:52:23ZengNature PortfolioScientific Reports2045-23222022-09-0112111110.1038/s41598-022-19975-yBis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitorsAsif Rasool0Zahra Batool1Majid Khan2Sobia Ahsan Halim3Zahid Shafiq4Ahmed Temirak5Mohamed A. Salem6Tarik E. Ali7Ajmal Khan8Ahmed Al-Harrasi9Institute of Chemical Sciences, Bahauddin Zakariya UniversityInstitute of Chemical Sciences, Bahauddin Zakariya UniversityNatural and Medical Sciences Research Center, University of NizwaNatural and Medical Sciences Research Center, University of NizwaInstitute of Chemical Sciences, Bahauddin Zakariya UniversityNational Research Centre, Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research InstituteDepartment of Chemistry, Faculty of Science and Arts, King Khalid UniversityDepartment of Chemistry, Faculty of Science, King Khalid UniversityNatural and Medical Sciences Research Center, University of NizwaNatural and Medical Sciences Research Center, University of NizwaAbstract 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 (IC50 = 10.3 ± 0.62 µM), 3g (IC50 = 12.1 ± 1.01 µM), and 3h (IC50 = 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.https://doi.org/10.1038/s41598-022-19975-y |
| spellingShingle | Asif Rasool Zahra Batool Majid Khan Sobia Ahsan Halim Zahid Shafiq Ahmed Temirak Mohamed A. Salem Tarik E. Ali Ajmal Khan Ahmed Al-Harrasi Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-022-19975-y |
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