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Research Article
Ahmed Al-Harrasi
University of Nizwa
Corresponding Author
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Boswellic acids are genus specific to Boswellia; they are the principal biologically active compounds holding exceptionally potent anti-inflammatory activity. A series of new 1H-1,2,3-triazole tethered of 3-O-acetyl-β-boswellic acid (ABA, 1) and 3-O-acetyl-11-keto-β-boswellic acid (AKBA, 2) derivatives (10a-d and 11a-d) were synthesized and their carbonic anhydrase II (CA II) inhibitory activity was evaluated in vitro. All compounds were characterized by 1H NMR, 13C NMR, 2D NMR (HMBC, HSQC, COSY and NOESY) experiments, ESI-MS, and when applicable by 19F NMR spectroscopy (10b, 10c and 11b, 11c). This series has displayed a moderate to strong inhibition against CA II with IC50 values of 13.2–60.1 µM. All the active compounds were reported for the first time for their CA II inhibition potential. Kinetics studies on the most active inhibitors (5 and 10b) were carried out to investigate their mode of inhibition and to determine their inhibition constants Ki. Both compounds (5 and 10b) were found to be non-competitive inhibitors with Ki values of 10.40 ± 0.013 and 14.25 ± 0.017 µM, respectively. Molecular docking studies showed that all compounds were well accommodated in the allosteric site of CA II. The current study has demonstrated the usefulness of incorporating a 1H-1,2,3-triazole moiety into the boswellic acids skeleton.
Keywords
3-O-acetyl-β-boswellic acid, 3-O-acetyl-11-keto-β-boswellic acid, 1H-1,2,3-triazole analogues, carbonic anhydrase II, inhibitor, molecular docking
Figure 1
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Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
- GraphicalAbstract.jpg
- Onlinefloatimage4.png
Scheme 1. Reagents and conditions: (i) 1-bromo propanol, K2CO3, DMF, room temperature, 18h; (ii) TsCl, Et3N, dry DCM, DMAP, 0 °C to room temperature, 5 h; (iii) NaN3, DMF, 70 °C, 3 h; (iv) Alkyne (9a-d), CuI, Et3N, CH3CN, room temperature, 3 h.
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View the published article at Medicinal Chemistry Research.
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A new preprint design is coming!
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See the published version of this preprint at Medicinal Chemistry Research.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Ahmed Al-Harrasi
University of Nizwa
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Medicinal Chemistry Research.
Version 2
Posted 19 Feb, 2021
No community comments so far
Reviewers invited
Invitations sent on 17 Feb, 2021
Reviews received
Received 17 Feb, 2021
Editor assigned
On 10 Feb, 2021
First submitted
On 05 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Medicinal Chemistry
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Medicinal Chemistry Research.
Boswellic acids are genus specific to Boswellia; they are the principal biologically active compounds holding exceptionally potent anti-inflammatory activity. A series of new 1H-1,2,3-triazole tethered of 3-O-acetyl-β-boswellic acid (ABA, 1) and 3-O-acetyl-11-keto-β-boswellic acid (AKBA, 2) derivatives (10a-d and 11a-d) were synthesized and their carbonic anhydrase II (CA II) inhibitory activity was evaluated in vitro. All compounds were characterized by 1H NMR, 13C NMR, 2D NMR (HMBC, HSQC, COSY and NOESY) experiments, ESI-MS, and when applicable by 19F NMR spectroscopy (10b, 10c and 11b, 11c). This series has displayed a moderate to strong inhibition against CA II with IC50 values of 13.2–60.1 µM. All the active compounds were reported for the first time for their CA II inhibition potential. Kinetics studies on the most active inhibitors (5 and 10b) were carried out to investigate their mode of inhibition and to determine their inhibition constants Ki. Both compounds (5 and 10b) were found to be non-competitive inhibitors with Ki values of 10.40 ± 0.013 and 14.25 ± 0.017 µM, respectively. Molecular docking studies showed that all compounds were well accommodated in the allosteric site of CA II. The current study has demonstrated the usefulness of incorporating a 1H-1,2,3-triazole moiety into the boswellic acids skeleton.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
- GraphicalAbstract.jpg
- Onlinefloatimage4.png
Scheme 1. Reagents and conditions: (i) 1-bromo propanol, K2CO3, DMF, room temperature, 18h; (ii) TsCl, Et3N, dry DCM, DMAP, 0 °C to room temperature, 5 h; (iii) NaN3, DMF, 70 °C, 3 h; (iv) Alkyne (9a-d), CuI, Et3N, CH3CN, room temperature, 3 h.
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