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.
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