Chemical and Antiplasmodial Investigations on Eremophila-Derived Alkaloids and Semisynthetic Ether Analogues
Microthecaline A (1), the known antiplasmodial quinoline serrulatane alkaloid from the roots of Eremophila microtheca F. Muell. ex Benth. (Scrophulariaceae), was targeted for isolation and subsequent use in the generation of a semisynthetic ether library. A large-scale extraction and isolation yielded the previously undescribed quinoline serrulatane microthecaline B (2), along with crystalline 1 that enabled the first X-ray crystallographic analysis to be undertaken on this rare alkaloid structure class. The X-ray diffraction analysis of 1 supported the absolute configuration assignment of microthecaline A, which was originally assigned by ECD data analysis. Microthecaline A (1) was converted into 10 new semisynthetic ether derivatives (3-12) using a diverse series of commercially available alkyl halides. Chemical structures of the new serrulatane alkaloid and semisynthetic ether analogues were assigned by spectroscopic and spectrometric analyses. Antiplasmodial evaluations of 1-12 showed that the semisynthetic derivative 5 elicited the most potent activity with an IC50 value of 7.2 μM against Plasmodium falciparum 3D7 (drug-sensitive) strain.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:87 |
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| Enthalten in: |
Journal of natural products - 87(2024), 4 vom: 26. Apr., Seite 849-854 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Chen [VerfasserIn] |
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| Links: |
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| Themen: |
Alkaloids |
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| Anmerkungen: |
Date Completed 26.04.2024 Date Revised 26.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jnatprod.3c01072 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369059492 |
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| 500 | |a Date Completed 26.04.2024 | ||
| 500 | |a Date Revised 26.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Microthecaline A (1), the known antiplasmodial quinoline serrulatane alkaloid from the roots of Eremophila microtheca F. Muell. ex Benth. (Scrophulariaceae), was targeted for isolation and subsequent use in the generation of a semisynthetic ether library. A large-scale extraction and isolation yielded the previously undescribed quinoline serrulatane microthecaline B (2), along with crystalline 1 that enabled the first X-ray crystallographic analysis to be undertaken on this rare alkaloid structure class. The X-ray diffraction analysis of 1 supported the absolute configuration assignment of microthecaline A, which was originally assigned by ECD data analysis. Microthecaline A (1) was converted into 10 new semisynthetic ether derivatives (3-12) using a diverse series of commercially available alkyl halides. Chemical structures of the new serrulatane alkaloid and semisynthetic ether analogues were assigned by spectroscopic and spectrometric analyses. Antiplasmodial evaluations of 1-12 showed that the semisynthetic derivative 5 elicited the most potent activity with an IC50 value of 7.2 μM against Plasmodium falciparum 3D7 (drug-sensitive) strain | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antimalarials |2 NLM | |
| 650 | 7 | |a Alkaloids |2 NLM | |
| 650 | 7 | |a Quinolines |2 NLM | |
| 650 | 7 | |a Ethers |2 NLM | |
| 700 | 1 | |a Lum, Kah Yean |e verfasserin |4 aut | |
| 700 | 1 | |a White, Jonathan M |e verfasserin |4 aut | |
| 700 | 1 | |a Duffy, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Lock, Aaron M |e verfasserin |4 aut | |
| 700 | 1 | |a Avery, Vicky M |e verfasserin |4 aut | |
| 700 | 1 | |a Davis, Rohan A |e verfasserin |4 aut | |
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