To discover the new medical entity from edible marine algae, our continuously natural product investigation focused on endophytes from marine macroalgae Grateloupia sp. Two new azaphilones, 8a-epi-hypocrellone A (1), 8a-epi-eupenicilazaphilone C (2), together with five known azaphilones, hypocrellone A (3), eupenicilazaphilone C (4), ((1E,3E)-3,5-dimethylhepta-1,3-dien-1-yl)-2,4-dihydroxy-3-methylbenzaldehyde (5), sclerotiorin (6), and isochromophilone IV (7) were isolated from the alga-derived fungus Penicillium sclerotiorum. The structures of isolated azaphilones (1–7) were elucidated by spectrometric identification, especially HRESIMS, CD, and NMR data analyses. Concerning bioactivity, cytotoxic, anti-inflammatory, and anti-fibrosis activities of those isolates were evaluated. As a result, compound 1 showed selective toxicity toward neuroblastoma cell line SH-SY5Y among seven cancer and one fibroblast cell lines. 20 μM of compounds 1, 3, and 7 inhibited the TNF-α-induced NFκB phosphorylation but did not change the NFκB activity. Compounds 2 and 6 respectively promoted and inhibited SMAD-mediated transcriptional activities stimulated by TGF-β.

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Four new alkaloids, hippobrines A−D (1−4), along with three new polyacetylenes, hippobrenes A−C (5−7), were isolated from Hippobroma longif lora. Compounds 1−3 possess an unprecedented carbon skeleton. All of the new structures were determined by analyzing their mass and NMR spectroscopic data. The absolute configurations of 1 and 2 were confirmed by singlecrystal X-ray analyses, and the absolute configurations of 3 and 7 were deduced using their ECD spectra. Plausible biogenetic pathways of 1 and 4 were proposed. In regard to bioactivities, all compounds (1−7) exhibited weak antiangiogenic activity against human endothelial progenitor cells, with IC 50 values ranging from 21.1 ± 1.1 to 44.0 ± 2.3 μg/mL.

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.