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

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 mu M 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.

Automated summary

Three new alkaloids were discovered from the whole plant of Hippobroma longiflora, along with five known compounds. The structures of the alkaloids were determined using various spectroscopic techniques. The neuroprotective effects of three major secondary metabolites were also evaluated.