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.

Five new metabolites, including three cyclic dipeptide derivatives (1–3) and two new polyketides (10–11), together with nine known ones (4–9 and 12–15), were isolated from the mangrove-sediments-derived fungus Talaromyces sp. SCSIO 41431. Their structures were determined using detailed NMR, MS spectroscopic analyses, and quantum chemical calculations. X-ray single-crystal diffraction analysis of 1 was described. Compounds 13–15 demonstrated activity against Staphylococcus aureus, with MIC values ranging from 25 to 50 µg/mL. Compound 9 showed activity against Escherichia coli, Streptococcus suis, and Erysipelothrix rhusiopathiae, with an MIC value of 100 µg/mL. In addition, compounds 1 and 12 showed DPPH radical scavenging activity, with the EC₅₀ of 27.62 and 29.34 µg/mL, compared to the positive control (ascorbic acid, EC₅₀, 12.74 µg/mL).

Sixteen polyketides, including six new compounds (1–2, and 5–8), were isolated from the culture of the marine sponge-associated fungus Neopestalotiopsis sp. SCSIO 41422. Their structures were elucidated through NMR, MS spectroscopic analyses, calculated electronic circular dichroism, quantum chemical NMR calculations, and X-ray single-crystal diffraction. To screen and evaluate the inhibitory activity of these polyketides in renal fibrosis, a TGF-β1-stimulated HK-2 cell model was used. All tested compounds (1, 5–8, and 11–12) at 10 µM showed obvious anti-fibrotic activity by inhibiting TGF-β1-induced α-SMA expression and extracellular matrix production (collagen I and fibronectin). Among them, gamahorin A (1) was shown to be the most potent and the most promising inhibitor against renal fibrosis.