New synthetic 1H-1,2,3-triazole derivatives of 3-O-acetyl-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid from Boswellia sacra inhibit carbonic anhydrase II in vitro

Abstract

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. The structures of all compounds were confirmed by 1H-, 13C-NMR, and HR-MS spectral data (10b, 10c and 11b, 11c). The series displayed a moderate to significant 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. After preliminary screening, kinetic studies of 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 revealed 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.