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Planta Med 2023; 89(03): 308-315
DOI: 10.1055/a-1903-2663
Biological and Pharmacological Activity
Original Papers

2,6-Disubstituted Piperidine Alkaloids with Neuroprotective Activity from Hippobroma longiflora

Shu-Rong Chen
1   Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan
,
Yih-Fung Chen
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
3   Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
,
Jue-Jun Lin
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
,
Tzu-Yi Ke
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
,
Yun-Sheng Lin
4   Department of Biological Science and Technology, Meiho University, Pingtung, Taiwan
,
Yuan-Bin Cheng
1   Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan
› Author AffiliationsSupported by: Ministry of Science and Technology, Taiwan Assistant Professor Yih-Fung Chen/108-2320-B-037-0
Supported by: Ministry of Science and Technology, Taiwan Professor Yuan-Bin Cheng/110-2628-B-110-005
Supported by: Ministry of Science and Technology, Taiwan Professor Yuan-Bin Cheng/1109-2628-B-110-004
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Abstract

Three new alkaloids, hipporidine A (1), hipporidine B (2), and (−)-lobeline N-oxide (3), were discovered from the whole plant of Hippobroma longiflora together with five known compounds (4–8). Their 2,6-disubstituted piperidine structures were established based on the HRESIMS, NMR (COSY, HMBC, HSQC, NOESY), and UV spectroscopic data. Hipporidines A (1) and B (2) possess a rare 1,3-oxazinane moiety. Compound 3 is the N-oxide derivative of (−)-lobeline (6). Moreover, the absolute configuration of norlobeline (5) was established by single-crystal X-ray diffraction analysis. Three major secondary metabolites (6–8) were evaluated for their neuroprotective effect against paclitaxel-induced neurotoxicity. Consequently, pretreatment with compound 8 at a concentration of 1.0 µM displayed significant attenuation on paclitaxel-damaged neurite outgrowth of dorsal root ganglion neurons without interfering with the cytotoxicity of paclitaxel on cervical cancer SiHa cells.

Key words

Hippobroma longiflora - Campanulaceae - alkaloids - neuroprotective activity

Supporting Information

    HRESIMS, IR, NMR (1H, 13C, COSY, HSQC, HMBC, and NOESY), and UV spectra of compounds 1–3, 1H and 13C NMR spectra of compounds 5 and 7, and X-ray crystallographic data of 5 are available as Supporting Information.

  • Supporting Information


Publication History

Received: 23 March 2022

Accepted after revision: 17 June 2022

Article published online:
08 December 2022

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