Biochemical and in silico inhibition of bovine and human carbonic anhydrase-II by 1H-1,2,3-triazole analogs
A series of 1H-1,2,3-triazole analogs (7a–7d and 9a–9s) were synthesized via “click” chemistry and evaluated for in vitro carbonic anhydrase-II (bovine and human) inhibitory activity. The synthesis of intermediates, 7a and 7c, was achieved by using (S)-(-)ethyl lactate as a starting material. These...
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Frontiers Media S.A.
2022-11-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.1072337/full |
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| author | Majid Khan Majid Khan Satya Kumar Avula Sobia Ahsan Halim Muhammad Waqas Mufarreh Asmari Ajmal Khan Ahmed Al-Harrasi |
| author_facet | Majid Khan Majid Khan Satya Kumar Avula Sobia Ahsan Halim Muhammad Waqas Mufarreh Asmari Ajmal Khan Ahmed Al-Harrasi |
| author_sort | Majid Khan |
| collection | DOAJ |
| description | A series of 1H-1,2,3-triazole analogs (7a–7d and 9a–9s) were synthesized via “click” chemistry and evaluated for in vitro carbonic anhydrase-II (bovine and human) inhibitory activity. The synthesis of intermediates, 7a and 7c, was achieved by using (S)-(-)ethyl lactate as a starting material. These compounds (7a and 7c) underwent Suzuki–Miyaura cross-coupling reaction with different arylboronic acids in 1,4-dioxane, reflux at 90–120°C for 8 h using Pd(PPh3)4 as a catalyst (5 mol%), and K2CO3 (3.0 equiv)/K2PO4 (3.0 equiv) as a base to produce target 1H-1,2,3-triazole molecules (9a–9s) for a good yield of 67–86%. All the synthesized compounds were characterized through NMR spectroscopic techniques. Furthermore, all those compounds have shown significant inhibitory potential for both sources of carbonic anhydrase-II (CA-II). In the case of bCA-II, compounds 9i, 7d, 9h, 9o, 9g, and 9e showed potent activity with IC50 values in the range of 11.1–17.8 µM. Whereas for hCA-II, compounds 9i, 9c, 9o, and 9j showed great potential with IC50 values in the range of 10.9–18.5 µM. The preliminary structure–activity relationship indicates that the presence of the 1H-1,2,3-triazole moiety in those synthesized 1H-1,2,3-triazole analogs (7a–7d and 9a–9s) significantly contributes to the overall activity. However, several substitutions on this scaffold affect the activity to several folds. The selectivity index showed that compounds 9c, 9k, and 9p are selective inhibitors of hCA-II. Kinetics studies showed that these compounds inhibited both enzymes (bCA-II and hCA-II) in a competitive manner. Molecular docking indicates that all the active compounds fit well in the active site of CA-II. This study has explored the role of 1H-1,2,3-triazole-containing compounds in the inhibition of CA-II to combat CA-II-related disorders. |
| first_indexed | 2024-04-13T08:14:42Z |
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| institution | Directory Open Access Journal |
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| last_indexed | 2024-04-13T08:14:42Z |
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| spelling | doaj.art-62e256760c73431db2689a007b8df5da2022-12-22T02:54:51ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-11-011010.3389/fchem.2022.10723371072337Biochemical and in silico inhibition of bovine and human carbonic anhydrase-II by 1H-1,2,3-triazole analogsMajid Khan0Majid Khan1Satya Kumar Avula2Sobia Ahsan Halim3Muhammad Waqas4Mufarreh Asmari5Ajmal Khan6Ahmed Al-Harrasi7Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, Nizwa, OmanH.E.J Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, PakistanNatural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, Nizwa, OmanNatural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, Nizwa, OmanNatural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, Nizwa, OmanDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, Saudi ArabiaNatural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, Nizwa, OmanNatural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, Nizwa, OmanA series of 1H-1,2,3-triazole analogs (7a–7d and 9a–9s) were synthesized via “click” chemistry and evaluated for in vitro carbonic anhydrase-II (bovine and human) inhibitory activity. The synthesis of intermediates, 7a and 7c, was achieved by using (S)-(-)ethyl lactate as a starting material. These compounds (7a and 7c) underwent Suzuki–Miyaura cross-coupling reaction with different arylboronic acids in 1,4-dioxane, reflux at 90–120°C for 8 h using Pd(PPh3)4 as a catalyst (5 mol%), and K2CO3 (3.0 equiv)/K2PO4 (3.0 equiv) as a base to produce target 1H-1,2,3-triazole molecules (9a–9s) for a good yield of 67–86%. All the synthesized compounds were characterized through NMR spectroscopic techniques. Furthermore, all those compounds have shown significant inhibitory potential for both sources of carbonic anhydrase-II (CA-II). In the case of bCA-II, compounds 9i, 7d, 9h, 9o, 9g, and 9e showed potent activity with IC50 values in the range of 11.1–17.8 µM. Whereas for hCA-II, compounds 9i, 9c, 9o, and 9j showed great potential with IC50 values in the range of 10.9–18.5 µM. The preliminary structure–activity relationship indicates that the presence of the 1H-1,2,3-triazole moiety in those synthesized 1H-1,2,3-triazole analogs (7a–7d and 9a–9s) significantly contributes to the overall activity. However, several substitutions on this scaffold affect the activity to several folds. The selectivity index showed that compounds 9c, 9k, and 9p are selective inhibitors of hCA-II. Kinetics studies showed that these compounds inhibited both enzymes (bCA-II and hCA-II) in a competitive manner. Molecular docking indicates that all the active compounds fit well in the active site of CA-II. This study has explored the role of 1H-1,2,3-triazole-containing compounds in the inhibition of CA-II to combat CA-II-related disorders.https://www.frontiersin.org/articles/10.3389/fchem.2022.1072337/fullsynthesisSuzuki–Miyaura cross-coupling“click” chemistry1H-1,2,3-triazole analogscarbonic anhydrase-II inhibitory activitymolecular docking studies |
| spellingShingle | Majid Khan Majid Khan Satya Kumar Avula Sobia Ahsan Halim Muhammad Waqas Mufarreh Asmari Ajmal Khan Ahmed Al-Harrasi Biochemical and in silico inhibition of bovine and human carbonic anhydrase-II by 1H-1,2,3-triazole analogs Frontiers in Chemistry synthesis Suzuki–Miyaura cross-coupling “click” chemistry 1H-1,2,3-triazole analogs carbonic anhydrase-II inhibitory activity molecular docking studies |
| title | Biochemical and in silico inhibition of bovine and human carbonic anhydrase-II by 1H-1,2,3-triazole analogs |
| title_full | Biochemical and in silico inhibition of bovine and human carbonic anhydrase-II by 1H-1,2,3-triazole analogs |
| title_fullStr | Biochemical and in silico inhibition of bovine and human carbonic anhydrase-II by 1H-1,2,3-triazole analogs |
| title_full_unstemmed | Biochemical and in silico inhibition of bovine and human carbonic anhydrase-II by 1H-1,2,3-triazole analogs |
| title_short | Biochemical and in silico inhibition of bovine and human carbonic anhydrase-II by 1H-1,2,3-triazole analogs |
| title_sort | biochemical and in silico inhibition of bovine and human carbonic anhydrase ii by 1h 1 2 3 triazole analogs |
| topic | synthesis Suzuki–Miyaura cross-coupling “click” chemistry 1H-1,2,3-triazole analogs carbonic anhydrase-II inhibitory activity molecular docking studies |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.1072337/full |
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