Two new chlorinated metabolites, 8-chlorine-5-hydroxy-2,3-dimethyl-7-methoxychromone (1) and 3,4-dichloro-1H-pyrrole-2,5-dione (3), and eight known compounds (2 and 4–9) were isolated from the mangrove sediments-derived fungus Mollisia sp. SCSIO41409. Their structures were elucidated by physicochemical properties and extensive spectroscopic analysis. The absolute configuration of stemphone C (4) was established for the first time by the X-ray crystallographic analysis. Compounds 3 and 4 showed different intensity of antimicrobial activities against several pathogenic fungi and bacteria, and antiproliferative activities against two human prostate cancer cell lines (IC₅₀ values 2.77 to 9.60 μM). Further, stemphone C (4) showed a reducing PC-3 cell colony formation, inducing apoptosis and blocking the cell cycle at S-phase in a dose-dependent manner; thus, it could be considered as a potential antiproliferative agent and a promising anti-prostate cancer lead compound.

A growing body of evidence indicates that glycosylated natural products have become vital platforms for the development of many existing first-line drugs. This review covers 205 new glycosides over the last 22 years (1997–2018), from marine microbes, including bacteria, cyanobacteria, and fungi. Herein, we discuss the structures and biological activities of these compounds, as well as the details of their source organisms.

Ten polyketide derivatives (1–10), including a new natural product named (E)-2,4-dihydroxy-3-methyl-6-(2-oxopent-3-en-1-yl) benzaldehyde (1), and five known diketopiperazines (11–15), were isolated from the mangrove-sediment-derived fungus Aspergillus sp. SCSIO41407. The structures of 1–15 were determined via NMR and MS spectroscopic analysis. In a variety of bioactivity screening, 3 showed weak cytotoxicity against the A549 cell line, and 2 exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Compounds 3, 5, and 6 showed inhibition against acetylcholinesterase (AChE) with IC₅₀ values of 23.9, 39.9, and 18.6 μM. Compounds 11, 12, and 14 exhibited obvious inhibitory activities of lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) with IC₅₀ values of 19.2, 20.9, and 8.7 μM, and they also suppressed RANKL-induced osteoclast differentiation in bone marrow macrophages cells (BMMCs), with the concentration of 5 μM. In silico molecular docking with AChE and NF-κB p65 protein were also performed to understand the inhibitory activities, and 1, 11–14 showed obvious protein/ligand-binding effects to the NF-κB p65 protein.

To discover bioactive natural products from mangrove sediment-derived microbes, a chemical investigation of the two Beibu Gulf-derived fungi strains, Talaromyces sp. SCSIO 41050 and Penicillium sp. SCSIO 41411, led to the isolation of 23 natural products. Five of them were identified as new ones, including two polyketide derivatives with unusual acid anhydride moieties named cordyanhydride A ethyl ester (1) and maleicanhydridane (4), and three hydroxyphenylacetic acid derivatives named stachylines H–J (10–12). Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses, while the absolute configurations were established by theoretical electronic circular dichroism (ECD) calculation. A variety of bioactive screens revealed three polyketide derivatives (1–3) with obvious antifungal activities, and 4 displayed moderate cytotoxicity against cell lines A549 and WPMY-1. Compounds 1 and 6 at 10 μM exhibited obvious inhibition against phosphodiesterase 4 (PDE4) with inhibitory ratios of 49.7% and 39.6%, respectively, while 5, 10, and 11 showed the potential of inhibiting acetylcholinesterase (AChE) by an enzyme activity test, as well as in silico docking analysis.

Two new sesquiterpenoid derivatives, elgonenes M (1) and N (2), and a new shikimic acid metabolite, methyl 5-O-acetyl-5-epi-shikimate (3), were isolated from the mangrove sediment-derived fungus Roussoella sp. SCSIO 41427 together with fourteen known compounds (4–17). The planar structures were elucidated through nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses. The relative configurations of 1–3 were ascertained by NOESY experiments, while their absolute configurations were determined by electronic circular dichroism (ECD) calculation. Elgonene M (1) exhibited inhibition of interleukin-1β (IL-1β) mRNA, a pro-inflammatory cytokine, at a concentration of 5 μM, with an inhibitory ratio of 31.14%. On the other hand, elgonene N (2) demonstrated inhibition at a concentration of 20 μM, with inhibitory ratios of 27.57%.

Three new polyketides, including three ester derivatives (1, 3, and 5) and a new natural product, which was a benzoquinone derivative, embelin A (4), together with nine known ones (2 and 6–13), were isolated from the mangrove-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by detailed NMR and MS spectroscopic analyses. The X-ray single-crystal diffraction analysis of 4 was described for the first time. Compound 9 displayed obvious inhibition against PDE4 with an inhibitory ratio of 40.78% at 10 μM. Compound 12 showed DPPH radical scavenging activity, with an EC₅₀ of 16.21 µg/mL, compared to the positive control (ascorbic acid, EC₅₀, 11.22 µg/mL). Furthermore, compound 4 exhibited cytotoxicity against PC-3 and LNCaP with IC₅₀ values of 18.69 and 31.62 µM, respectively.