Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from <i>Boswellia elongata</i> with Structure-Activity Relationship: In Vitro and In Silico Studies
Fourteen triterpene acids, viz., three tirucallane-type (<b>1</b>–<b>3</b>), eight ursane-type (<b>4</b>–<b>11</b>), two oleanane-type (<b>12</b>, <b>13</b>) and one lupane type (<b>21</b>), along with boswellic alde...
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MDPI AG
2020-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/5/751 |
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| author | Najeeb Ur Rehman Sobia Ahsan Halim Mohammed Al-Azri Majid Khan Ajmal Khan Kashif Rafiq Ahmed Al-Rawahi Rene Csuk Ahmed Al-Harrasi |
| author_facet | Najeeb Ur Rehman Sobia Ahsan Halim Mohammed Al-Azri Majid Khan Ajmal Khan Kashif Rafiq Ahmed Al-Rawahi Rene Csuk Ahmed Al-Harrasi |
| author_sort | Najeeb Ur Rehman |
| collection | DOAJ |
| description | Fourteen triterpene acids, viz., three tirucallane-type (<b>1</b>–<b>3</b>), eight ursane-type (<b>4</b>–<b>11</b>), two oleanane-type (<b>12</b>, <b>13</b>) and one lupane type (<b>21</b>), along with boswellic aldehyde (<b>14</b>), α-amyrine (<b>15</b>), epi-amyrine (<b>16</b>), straight chain acid (<b>17</b>), sesquiterpene (<b>19</b>) and two cembrane-type diterpenes (<b>18</b>, <b>20</b>) were isolated, first time, from the methanol extract of <i>Boswellia elongata</i> resin. Compound (<b>1</b>) was isolated for first time as a natural product, while the remaining compounds (<b>2</b>‒<b>21</b>) were reported for first time from <i>B. elongata.</i> The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (<b>1</b>–<b>5, 11, 19</b> and <b>20</b>) were further screened for in vitro α-glucosidase inhibitory activity. Compounds <b>3</b>–<b>5</b> and <b>11</b> showed significant activity against α-glucosidase with IC<sub>50</sub> values ranging from 9.9–56.8 μM. Compound <b>4</b> (IC<sub>50</sub> = 9.9 ± 0.48 μM) demonstrated higher inhibition followed by <b>11</b> (IC<sub>50</sub> = 14.9 ± 1.31 μM), <b>5</b> (IC<sub>50</sub> = 20.9 ± 0.05 μM) and <b>3</b> (IC<sub>50</sub> = 56.8 ± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds <b>3</b>–<b>5</b> and <b>11</b> were carried out to investigate their mechanism (mode of inhibition and dissociation constants <i>K<sub>i</sub></i>). All compounds were found to be non-competitive inhibitors with <i>K<sub>i</sub></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. |
| first_indexed | 2024-03-10T19:53:05Z |
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| language | English |
| last_indexed | 2024-03-10T19:53:05Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-ec6fa3ec810440e59af756481e561e8c2023-11-20T00:12:29ZengMDPI AGBiomolecules2218-273X2020-05-0110575110.3390/biom10050751Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from <i>Boswellia elongata</i> with Structure-Activity Relationship: In Vitro and In Silico StudiesNajeeb Ur Rehman0Sobia Ahsan Halim1Mohammed Al-Azri2Majid Khan3Ajmal Khan4Kashif Rafiq5Ahmed Al-Rawahi6Rene Csuk7Ahmed Al-Harrasi8Natural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanOrganic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), GermanyNatural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanFourteen triterpene acids, viz., three tirucallane-type (<b>1</b>–<b>3</b>), eight ursane-type (<b>4</b>–<b>11</b>), two oleanane-type (<b>12</b>, <b>13</b>) and one lupane type (<b>21</b>), along with boswellic aldehyde (<b>14</b>), α-amyrine (<b>15</b>), epi-amyrine (<b>16</b>), straight chain acid (<b>17</b>), sesquiterpene (<b>19</b>) and two cembrane-type diterpenes (<b>18</b>, <b>20</b>) were isolated, first time, from the methanol extract of <i>Boswellia elongata</i> resin. Compound (<b>1</b>) was isolated for first time as a natural product, while the remaining compounds (<b>2</b>‒<b>21</b>) were reported for first time from <i>B. elongata.</i> The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (<b>1</b>–<b>5, 11, 19</b> and <b>20</b>) were further screened for in vitro α-glucosidase inhibitory activity. Compounds <b>3</b>–<b>5</b> and <b>11</b> showed significant activity against α-glucosidase with IC<sub>50</sub> values ranging from 9.9–56.8 μM. Compound <b>4</b> (IC<sub>50</sub> = 9.9 ± 0.48 μM) demonstrated higher inhibition followed by <b>11</b> (IC<sub>50</sub> = 14.9 ± 1.31 μM), <b>5</b> (IC<sub>50</sub> = 20.9 ± 0.05 μM) and <b>3</b> (IC<sub>50</sub> = 56.8 ± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds <b>3</b>–<b>5</b> and <b>11</b> were carried out to investigate their mechanism (mode of inhibition and dissociation constants <i>K<sub>i</sub></i>). All compounds were found to be non-competitive inhibitors with <i>K<sub>i</sub></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.https://www.mdpi.com/2218-273X/10/5/751<i>Boswellia elongata</i>triterpene acidsα-glucosidase inhibitorsNMR spectroscopykinetics studyhomology modeling |
| spellingShingle | Najeeb Ur Rehman Sobia Ahsan Halim Mohammed Al-Azri Majid Khan Ajmal Khan Kashif Rafiq Ahmed Al-Rawahi Rene Csuk Ahmed Al-Harrasi Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from <i>Boswellia elongata</i> with Structure-Activity Relationship: In Vitro and In Silico Studies Biomolecules <i>Boswellia elongata</i> triterpene acids α-glucosidase inhibitors NMR spectroscopy kinetics study homology modeling |
| title | Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from <i>Boswellia elongata</i> with Structure-Activity Relationship: In Vitro and In Silico Studies |
| title_full | Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from <i>Boswellia elongata</i> with Structure-Activity Relationship: In Vitro and In Silico Studies |
| title_fullStr | Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from <i>Boswellia elongata</i> with Structure-Activity Relationship: In Vitro and In Silico Studies |
| title_full_unstemmed | Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from <i>Boswellia elongata</i> with Structure-Activity Relationship: In Vitro and In Silico Studies |
| title_short | Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from <i>Boswellia elongata</i> with Structure-Activity Relationship: In Vitro and In Silico Studies |
| title_sort | triterpenic acids as non competitive α glucosidase inhibitors from i boswellia elongata i with structure activity relationship in vitro and in silico studies |
| topic | <i>Boswellia elongata</i> triterpene acids α-glucosidase inhibitors NMR spectroscopy kinetics study homology modeling |
| url | https://www.mdpi.com/2218-273X/10/5/751 |
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