Pimarane Diterpenoids from the Seeds of <i>Caesalpinia minax</i> as PTP1B Inhibitors and Insulin Sensitizers
Protein-tyrosine phosphatase 1B (PTP1B) has been considered as a promising target for treating insulin resistance. In searching for naturally occurring PTB1B antagonists, two new pimarane diterpenoids, named 2α-hydroxy-7-oxo-pimara-8(9),15-diene (<b>1</b>) and 19-hydroxy-2α-acetoxy-7-oxo...
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| Format: | Article |
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/20/4674 |
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| author | Yunshao Xu Zheling Feng Tian Zhang Peng Lv Jun Cao Dan Li Cheng Peng Ligen Lin |
| author_facet | Yunshao Xu Zheling Feng Tian Zhang Peng Lv Jun Cao Dan Li Cheng Peng Ligen Lin |
| author_sort | Yunshao Xu |
| collection | DOAJ |
| description | Protein-tyrosine phosphatase 1B (PTP1B) has been considered as a promising target for treating insulin resistance. In searching for naturally occurring PTB1B antagonists, two new pimarane diterpenoids, named 2α-hydroxy-7-oxo-pimara-8(9),15-diene (<b>1</b>) and 19-hydroxy-2α-acetoxy-7-oxo-pimara-8(9),15-diene (<b>2</b>), were isolated from the seeds of <i>Caesalpinia minax</i>. Their structures were determined by extensive analysis of NMR and HR-ESIMS data, and their absolute configurations were determined by electronic circular dichroism (ECD) spectra. Compound <b>1</b> was disclosed as a competitive inhibitor of PTP1B with an IC<sub>50</sub> (the half-maximal inhibitory concentration) value of 19.44 ± 2.39 µM and a <i>K</i>i (inhibition constant) value of 13.69 ± 2.72 μM. Moreover, compound <b>1</b> dose-dependently promoted insulin-stimulated glucose uptake in C2C12 myotubes through activating insulin signaling pathway. Compound <b>1</b> might be further developed as an insulin sensitizer. |
| first_indexed | 2024-03-10T15:39:26Z |
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| id | doaj.art-6616f0587b2b4890939eb925169ab4a8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:39:26Z |
| publishDate | 2020-10-01 |
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| series | Molecules |
| spelling | doaj.art-6616f0587b2b4890939eb925169ab4a82023-11-20T16:57:21ZengMDPI AGMolecules1420-30492020-10-012520467410.3390/molecules25204674Pimarane Diterpenoids from the Seeds of <i>Caesalpinia minax</i> as PTP1B Inhibitors and Insulin SensitizersYunshao Xu0Zheling Feng1Tian Zhang2Peng Lv3Jun Cao4Dan Li5Cheng Peng6Ligen Lin7State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, ChinaState Key Laboratory of Southwestern Characteristic Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, ChinaState Key Laboratory of Southwestern Characteristic Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, ChinaProtein-tyrosine phosphatase 1B (PTP1B) has been considered as a promising target for treating insulin resistance. In searching for naturally occurring PTB1B antagonists, two new pimarane diterpenoids, named 2α-hydroxy-7-oxo-pimara-8(9),15-diene (<b>1</b>) and 19-hydroxy-2α-acetoxy-7-oxo-pimara-8(9),15-diene (<b>2</b>), were isolated from the seeds of <i>Caesalpinia minax</i>. Their structures were determined by extensive analysis of NMR and HR-ESIMS data, and their absolute configurations were determined by electronic circular dichroism (ECD) spectra. Compound <b>1</b> was disclosed as a competitive inhibitor of PTP1B with an IC<sub>50</sub> (the half-maximal inhibitory concentration) value of 19.44 ± 2.39 µM and a <i>K</i>i (inhibition constant) value of 13.69 ± 2.72 μM. Moreover, compound <b>1</b> dose-dependently promoted insulin-stimulated glucose uptake in C2C12 myotubes through activating insulin signaling pathway. Compound <b>1</b> might be further developed as an insulin sensitizer.https://www.mdpi.com/1420-3049/25/20/4674pimarane diterpenoids<i>Caesalpinia minax</i>PTP1Bglucose uptakeC2C12 myotubes |
| spellingShingle | Yunshao Xu Zheling Feng Tian Zhang Peng Lv Jun Cao Dan Li Cheng Peng Ligen Lin Pimarane Diterpenoids from the Seeds of <i>Caesalpinia minax</i> as PTP1B Inhibitors and Insulin Sensitizers Molecules pimarane diterpenoids <i>Caesalpinia minax</i> PTP1B glucose uptake C2C12 myotubes |
| title | Pimarane Diterpenoids from the Seeds of <i>Caesalpinia minax</i> as PTP1B Inhibitors and Insulin Sensitizers |
| title_full | Pimarane Diterpenoids from the Seeds of <i>Caesalpinia minax</i> as PTP1B Inhibitors and Insulin Sensitizers |
| title_fullStr | Pimarane Diterpenoids from the Seeds of <i>Caesalpinia minax</i> as PTP1B Inhibitors and Insulin Sensitizers |
| title_full_unstemmed | Pimarane Diterpenoids from the Seeds of <i>Caesalpinia minax</i> as PTP1B Inhibitors and Insulin Sensitizers |
| title_short | Pimarane Diterpenoids from the Seeds of <i>Caesalpinia minax</i> as PTP1B Inhibitors and Insulin Sensitizers |
| title_sort | pimarane diterpenoids from the seeds of i caesalpinia minax i as ptp1b inhibitors and insulin sensitizers |
| topic | pimarane diterpenoids <i>Caesalpinia minax</i> PTP1B glucose uptake C2C12 myotubes |
| url | https://www.mdpi.com/1420-3049/25/20/4674 |
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