Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies

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

doi:10.3390/biom10050751

Open AccessArticle

Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies

by

Najeeb Ur Rehman

^1,†

,

Sobia Ahsan Halim

^1,†,

Mohammed Al-Azri

¹,

Majid Khan

^1,2,

Ajmal Khan

¹,

Kashif Rafiq

^1,3,

Ahmed Al-Rawahi

¹,

Rene Csuk

⁴

and

Ahmed Al-Harrasi

^1,*

¹

Natural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, Oman

²

H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan

³

Department of Chemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan

⁴

Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany

^*

Author to whom correspondence should be addressed.

^†

Both authors equally contribute.

Biomolecules 2020, 10(5), 751; https://doi.org/10.3390/biom10050751

Submission received: 16 March 2020 / Revised: 17 April 2020 / Accepted: 20 April 2020 / Published: 12 May 2020

(This article belongs to the Special Issue Enzymatic Inhibitors from Natural Sources: A Huge Collection of New Potential Drugs)

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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 K_i). All compounds were found to be non-competitive inhibitors with K_i 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.

Keywords: Boswellia elongata; triterpene acids; α-glucosidase inhibitors; NMR spectroscopy; kinetics study; homology modeling; molecular docking

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MDPI and ACS Style

Ur Rehman, N.; Halim, S.A.; Al-Azri, M.; Khan, M.; Khan, A.; Rafiq, K.; Al-Rawahi, A.; Csuk, R.; Al-Harrasi, A. Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies. Biomolecules 2020, 10, 751. https://doi.org/10.3390/biom10050751

AMA Style

Ur Rehman N, Halim SA, Al-Azri M, Khan M, Khan A, Rafiq K, Al-Rawahi A, Csuk R, Al-Harrasi A. Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies. Biomolecules. 2020; 10(5):751. https://doi.org/10.3390/biom10050751

Chicago/Turabian Style

Ur Rehman, Najeeb, Sobia Ahsan Halim, Mohammed Al-Azri, Majid Khan, Ajmal Khan, Kashif Rafiq, Ahmed Al-Rawahi, Rene Csuk, and Ahmed Al-Harrasi. 2020. "Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies" Biomolecules 10, no. 5: 751. https://doi.org/10.3390/biom10050751

APA Style

Ur Rehman, N., Halim, S. A., Al-Azri, M., Khan, M., Khan, A., Rafiq, K., Al-Rawahi, A., Csuk, R., & Al-Harrasi, A. (2020). Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies. Biomolecules, 10(5), 751. https://doi.org/10.3390/biom10050751

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Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies

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