Bis-Iridoid Glycosides and Triterpenoids from <i>Kolkwitzia amabilis</i> and Their Potential as Inhibitors of ACC1 and ACL
A comprehensive phytochemical investigation of the twigs/leaves and flower buds of <i>Kolkwitzia amabilis</i>, a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (<b>1</b>–<b>4...
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2024-12-01
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| author | Jiang Wan Ze-Yu Zhao Can Wang Chun-Xiao Jiang Ying-Peng Tong Yi Zang Yeun-Mun Choo Jia Li Jin-Feng Hu |
| author_facet | Jiang Wan Ze-Yu Zhao Can Wang Chun-Xiao Jiang Ying-Peng Tong Yi Zang Yeun-Mun Choo Jia Li Jin-Feng Hu |
| author_sort | Jiang Wan |
| collection | DOAJ |
| description | A comprehensive phytochemical investigation of the twigs/leaves and flower buds of <i>Kolkwitzia amabilis</i>, a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (<b>1</b>–<b>4</b> and <b>7</b>–<b>13</b>), 20 triterpenoids (<b>5</b>, <b>6</b>, and <b>14</b>–<b>31</b>), and 8 phenylpropanoids (<b>32</b>–<b>39</b>). Among these, amabiliosides A (<b>1</b>) and B (<b>2</b>) represent previously undescribed bis-iridoid glycosides, while amabiliosides C (<b>3</b>) and D (<b>4</b>) feature a unique bis-iridoid-monoterpenoid indole alkaloid scaffold with a tetrahydro-<i>β</i>-carboline-5-carboxylic acid moiety. Amabiliacids A (<b>5</b>) and B (<b>6</b>) are 24-nor-ursane-type triterpenoids characterized by an uncommon ∆<sup>11,13(18)</sup> transannular double bond. Their chemical structures and absolute configurations were elucidated through spectroscopic data and electronic circular dichroism analyses. Compound <b>2</b> exhibited a moderate inhibitory effect against acetyl CoA carboxylase 1 (ACC1), with an IC<sub>50</sub> value of 9.6 μM. Lonicejaposide C (<b>8</b>), 3<i>β</i>-<i>O</i>-<i>trans</i>-caffeoyl-olean-12-en-28-oic acid (<b>29</b>), and (23<i>E</i>)-coumaroylhederagenin (<b>31</b>) showed notable inhibitory effects on ATP-citrate lyase (ACL), with IC<sub>50</sub> values of 3.6, 1.6, and 4.7 μM, respectively. Additionally, 3<i>β</i>-acetyl-ursolic acid (<b>17</b>) demonstrated dual inhibitory activity against both ACC1 and ACL, with IC<sub>50</sub> values of 10.3 and 2.0 μM, respectively. The interactions of the active compounds with ACC1 and ACL enzymes were examined through molecular docking studies. From a chemotaxonomic perspective, the isolation of bis-iridoid glycosides in this study may aid in clarifying the taxonomic relationship between the genera <i>Kolkwitzia</i> and <i>Lonicera</i> within the Caprifoliaceae family. These findings highlight the importance of conserving plant species with unique and diverse secondary metabolites, which could serve as potential sources of new therapeutic agents for treating ACC1/ACL-associated diseases. |
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| spelling | doaj-art-3ca05a3606b74d15b7675f3b1ecfc0952025-08-20T02:43:49ZengMDPI AGMolecules1420-30492024-12-012924598010.3390/molecules29245980Bis-Iridoid Glycosides and Triterpenoids from <i>Kolkwitzia amabilis</i> and Their Potential as Inhibitors of ACC1 and ACLJiang Wan0Ze-Yu Zhao1Can Wang2Chun-Xiao Jiang3Ying-Peng Tong4Yi Zang5Yeun-Mun Choo6Jia Li7Jin-Feng Hu8Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Pharmaceutical Sciences, Taizhou University, Taizhou 318000, ChinaZhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Pharmaceutical Sciences, Taizhou University, Taizhou 318000, ChinaZhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Pharmaceutical Sciences, Taizhou University, Taizhou 318000, ChinaZhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Pharmaceutical Sciences, Taizhou University, Taizhou 318000, ChinaZhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Pharmaceutical Sciences, Taizhou University, Taizhou 318000, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaChemistry Department, Faculty of Science, University of Malaya, Kuala Lumpur 50603, MalaysiaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaZhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Pharmaceutical Sciences, Taizhou University, Taizhou 318000, ChinaA comprehensive phytochemical investigation of the twigs/leaves and flower buds of <i>Kolkwitzia amabilis</i>, a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (<b>1</b>–<b>4</b> and <b>7</b>–<b>13</b>), 20 triterpenoids (<b>5</b>, <b>6</b>, and <b>14</b>–<b>31</b>), and 8 phenylpropanoids (<b>32</b>–<b>39</b>). Among these, amabiliosides A (<b>1</b>) and B (<b>2</b>) represent previously undescribed bis-iridoid glycosides, while amabiliosides C (<b>3</b>) and D (<b>4</b>) feature a unique bis-iridoid-monoterpenoid indole alkaloid scaffold with a tetrahydro-<i>β</i>-carboline-5-carboxylic acid moiety. Amabiliacids A (<b>5</b>) and B (<b>6</b>) are 24-nor-ursane-type triterpenoids characterized by an uncommon ∆<sup>11,13(18)</sup> transannular double bond. Their chemical structures and absolute configurations were elucidated through spectroscopic data and electronic circular dichroism analyses. Compound <b>2</b> exhibited a moderate inhibitory effect against acetyl CoA carboxylase 1 (ACC1), with an IC<sub>50</sub> value of 9.6 μM. Lonicejaposide C (<b>8</b>), 3<i>β</i>-<i>O</i>-<i>trans</i>-caffeoyl-olean-12-en-28-oic acid (<b>29</b>), and (23<i>E</i>)-coumaroylhederagenin (<b>31</b>) showed notable inhibitory effects on ATP-citrate lyase (ACL), with IC<sub>50</sub> values of 3.6, 1.6, and 4.7 μM, respectively. Additionally, 3<i>β</i>-acetyl-ursolic acid (<b>17</b>) demonstrated dual inhibitory activity against both ACC1 and ACL, with IC<sub>50</sub> values of 10.3 and 2.0 μM, respectively. The interactions of the active compounds with ACC1 and ACL enzymes were examined through molecular docking studies. From a chemotaxonomic perspective, the isolation of bis-iridoid glycosides in this study may aid in clarifying the taxonomic relationship between the genera <i>Kolkwitzia</i> and <i>Lonicera</i> within the Caprifoliaceae family. These findings highlight the importance of conserving plant species with unique and diverse secondary metabolites, which could serve as potential sources of new therapeutic agents for treating ACC1/ACL-associated diseases.https://www.mdpi.com/1420-3049/29/24/5980<i>Kolkwitzia amabilis</i>bis-iridoid glycosidestriterpenoidsacetyl CoA carboxylase 1ATP-citrate lyase |
| spellingShingle | Jiang Wan Ze-Yu Zhao Can Wang Chun-Xiao Jiang Ying-Peng Tong Yi Zang Yeun-Mun Choo Jia Li Jin-Feng Hu Bis-Iridoid Glycosides and Triterpenoids from <i>Kolkwitzia amabilis</i> and Their Potential as Inhibitors of ACC1 and ACL Molecules <i>Kolkwitzia amabilis</i> bis-iridoid glycosides triterpenoids acetyl CoA carboxylase 1 ATP-citrate lyase |
| title | Bis-Iridoid Glycosides and Triterpenoids from <i>Kolkwitzia amabilis</i> and Their Potential as Inhibitors of ACC1 and ACL |
| title_full | Bis-Iridoid Glycosides and Triterpenoids from <i>Kolkwitzia amabilis</i> and Their Potential as Inhibitors of ACC1 and ACL |
| title_fullStr | Bis-Iridoid Glycosides and Triterpenoids from <i>Kolkwitzia amabilis</i> and Their Potential as Inhibitors of ACC1 and ACL |
| title_full_unstemmed | Bis-Iridoid Glycosides and Triterpenoids from <i>Kolkwitzia amabilis</i> and Their Potential as Inhibitors of ACC1 and ACL |
| title_short | Bis-Iridoid Glycosides and Triterpenoids from <i>Kolkwitzia amabilis</i> and Their Potential as Inhibitors of ACC1 and ACL |
| title_sort | bis iridoid glycosides and triterpenoids from i kolkwitzia amabilis i and their potential as inhibitors of acc1 and acl |
| topic | <i>Kolkwitzia amabilis</i> bis-iridoid glycosides triterpenoids acetyl CoA carboxylase 1 ATP-citrate lyase |
| url | https://www.mdpi.com/1420-3049/29/24/5980 |
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