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Seven new 18-residue peptaibols, trichorzins A–G (1–7), were isolated from the sponge-derived fungus Trichodermasp. GXIMD 01001. Their structures and configurations were characterized by a comprehensive interpretation of the NMR spectroscopic data, MS/MS fragmentation, Marfey’s method, and ECD analysis. The general sequences of trichorzins A–G are as follows: Ac-Aib1-Ala/Ser2-Ala3-Aib/Iva4-Iva5-Gln6-Aib/Iva7-Val/allo-Ile8-Aib9-Gly10-Leu11-Aib12-Pro13-Leu14-Aib15-Aib16-Gln17-Trpol/Pheol18. The obtained compounds were assessed for their potential antiproliferative and antimicrobial activities. All obtained compounds did not show potent antibacterial activity but exhibited significant cytotoxicity, with the lowest IC50values at 0.46–4.7 μM against four human carcinoma cell lines.

Malaymycin (1), a new cyclopentenone-containing tetrahydroquinoline alkaloid, and mccrearamycin E (2), a geldanamycin analogue bearing a rare ring-contracted cyclopentenone moiety, and a C2-symmetric macrodiolide (7) were isolated from Streptomyces malaysiensisSCSIO41397. Their structures including absolute configurations were determined by detailed analyses of NMR and HRMS data and ECD calculations. The occurrence of mccrearamycin E (2) bearing a ring-contracted cyclopentenone is rare in the geldanamycin class. All isolated compounds were evaluated for their cytotoxicities against five cancer cell lines. As a result, compounds 1, 4, 5, and 7showed cytotoxicity against some or all of the five cancer cell lines with IC50values ranging from 0.067 to 7.2 μM. In particular, compound 1inhibited the growth of C42B and H446 cell lines with IC50values of 67 and 70 nM, respectively. Malaymycin (1) significantly induced cell cycle arrest at the G0/G1 phase in C42B cell lines and caused cell shrinkage and inhibited the expression of the androgen receptor (AR) at both the mRNA and protein levels in a dose-dependent manner. Further examination by qRT-PCR analysis showed that 1strongly suppressed the expression of AR target genes KLK2and KLK3in the C42B and 22RV1 cell lines, which suggested that 1might be a promising potential lead compound for the development of a treatment for the castration-resistant prostate cancer (CRPC).

Fungal linear polyketides, such as a-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (1and 2) and four known (3–6) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (alt) for alternapyrones was identified from A. arundinisZSDS-F3 and validated by heterologous expression in Aspergillus nidulansA1145 ?ST?EM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH3to a carboxyl group to produce 4from 3. Another cytochrome P450 monooxygenase, Alt3', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1, 2, 5, and 6from 4. Alternapyrone G (1) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aß treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer’s disease drug discovery.

Seven unusual new ene-yne hydroquinones (1–3, 5–8), including three rare glycosylated derivatives named pestalotioquinosides A–C (6–8), were obtained from the marine-derived strain SCSIO41403 of the fungus Pestalotiopsis neglecta. Their structures including absolute configurations were elucidated by spectroscopic analysis and induced electronic circular dichroism experiments. In silico molecular docking and in vitrosurface plasmon resonance studies showed that pestalotioquinoside C (8) could act as a liver X receptor alpha (LXRα) modulator. Further study showed that LXR target gene ABCA1was significantly upregulated by 8, which revealed 8as a potential LXRα agonist.

Six new highly oxygenated chloroazaphilone derivatives, isochromophilones A–F (1–6), were obtained from the mangrove-derived fungus Diaporthesp. SCSIO 41011, together with six known analogues (7–12). The structures of 1–6including absolute configurations were determined by detailed NMR, MS spectroscopic analyses, and electronic circular dichroism spectra. Compounds 1and 2represent the first reported azaphilones lacking a carbonyl group at C-6. Compound 8exhibited cytotoxic activities against three renal carcinoma cell lines, ACHN, OS-RC-2, and 786-O cells, with IC50values ranging from 3.0 to 4.4 μM, and 4showed activity against 786-O cells with an IC50of 8.9 μM. Further studies indicated that 4induced apoptosis in 786-O cells in a dose- and time-dependent manner.

Seven new tanzawaic acid derivatives, steckwaic acids E–K (1–7), and one new benzene derivate (8), together with seven known tanzawaic acid analogues (9–16) were isolated from the marine algicolous fungus Penicillium steckiiSCSIO 41040. The structures and absolute configurations of these new compounds (1–8) were determined by spectroscopic analyses, X-ray diffraction, and comparison of ECD spectra to calculations. Compounds 2, 10, and 15inhibited lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) with IC50values of 10.4, 18.6, and 15.2 μM, respectively. Compound 2could suppress the receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophage cells (BMMCs). To the best of our knowledge, this is the first report of osteoclastogenesis inhibitory activity for tanzawaic acid derivatives.

Five new highly oxygenated α-pyrone merosesquiterpenoids, ochraceopones A–E (1–5), together with one new double bond isomer of asteltoxin, isoasteltoxin (6), and two known asteltoxin derivatives, asteltoxin (7) and asteltoxin B (8), were isolated from an Antarctic soil-derived fungus, Aspergillus ochraceopetaliformisSCSIO 05702. Their structures were determined through extensive spectroscopic analysis, CD spectra, quantum mechanical calculations, and X-ray single-crystal diffraction. Ochraceopones A–D (1–4) are the first examples of α-pyrone merosesquiterpenoids possessing a linear tetracyclic carbon skeleton, which has not been previously described. All the isolated compounds were tested for their antiviral, cytotoxic, antibacterial, and antitubercular activities. Among these compounds, ochraceopone A (1), isoasteltoxin (6), and asteltoxin (7) exhibited antiviral activities against the H1N1 and H3N2 influenza viruses with IC50values of >20.0/12.2 ± 4.10, 0.23 ± 0.05/0.66 ± 0.09, and 0.54 ± 0.06/0.84 ± 0.02 μM, respectively. A possible biosynthetic pathway for ochraceopones A–E (1–5) was proposed.

Paeciloketals (1–3), new benzannulated spiroketal derivatives, were isolated from the marine fungus Paecilomyces variotiiderived from the giant jellyfish Nemopilema nomurai. Compound 1was present as a racemate and was resolved into enantiopure 1aand 1bby chiral-phase separation on a cellulose column. Compounds 2and 3, possessing a novel benzannulated spiroketal skeleton, were rapidly interconvertible and yielded an equilibrium mixture on standing at room temperature. The relative and absolute configurations of compounds 2and 3were determined by NOESY analysis and ECD calculations. Compound 1showed modest antibacterial activity against the marine pathogen Vibrio ichthyoenteri.

Strepsesquitriol, a new caged sesquiterpene, was isolated from Streptomycessp. SCSIO 10355. Its absolute structure was established as (1R,2R,4S,5S,8S,10S)-4,9,9,10-tetramethyl-2,5,10-trihydroxytricyclo[6.2.1.01,5]undecane by NMR analysis and a theoretical optical rotation derived from quantum-chemical calculations. It showed moderate inhibitory activity against lipopolysaccharide-induced TNFα production in RAW264.7 macrophages.