Triterpenic acids as non-competitive α-glucosidase inhibitors from boswellia elongata with structure-activity relationship: In vitro and in silico studies

Najeeb Ur Rehman, Sobia Ahsan Halim, Mohammed Al-Azri, Majid Khan, Ajmal Khan, Kashif Rafiq, Ahmed Al-Rawahi, Rene Csuk, Ahmed Al-Harrasi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Fourteen triterpene acids, viz., three tirucallane-type (1–3), eight ursane-type (4–11), two oleanane-type (12, 13) and one lupane type (21), along with boswellic aldehyde (14), α-amyrine (15), epi-amyrine (16), straight chain acid (17), sesquiterpene (19) and two cembrane-type diterpenes (18, 20) were isolated, first time, from the methanol extract of Boswellia elongata resin. Compound (1) was isolated for first time as a natural product, while the remaining compounds (2-21) were reported for first time from B. elongata. The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (1–5, 11, 19 and 20) were further screened for in vitro α-glucosidase inhibitory activity. Compounds 3–5 and 11 showed significant activity against α-glucosidase with IC50 values ranging from 9.9–56.8 µM. Compound 4 (IC50 = 9.9 ± 0.48 µM) demonstrated higher inhibition followed by 11 (IC50 = 14.9 ± 1.31 µM), 5 (IC50 = 20.9 ± 0.05 µM) and 3 (IC50 = 56.8 ± 1.30 µM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds 3–5 and 11 were carried out to investigate their mechanism (mode of inhibition and dissociation constants Ki ). All compounds were found to be non-competitive inhibitors with Ki values in the range of 7.05 ± 0.17–51.15 ± 0.25 µM. Moreover, in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase. The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities. Furthermore, the α-glucosidase inhibitory potential of the active compounds is reported here for the first time.

Original languageEnglish
Article number751
JournalBiomolecules
Volume10
Issue number5
DOIs
Publication statusPublished - May 2020
Externally publishedYes

Keywords

  • Boswellia elongata
  • Homology modeling
  • Kinetics study
  • Molecular docking
  • NMR spectroscopy
  • Triterpene acids
  • α-glucosidase inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this