Jian-Jun Chen

Seven novel phenyl-O-β-d-ribofuranoside derivatives (1–7), along with four known naphthalenones (8–11), were isolated from the endophytic fungus Neofusicoccum sp. LZUC-S1 using a bioactivity-guided isolation. Their chemical structures were elucidated through an integrated analysis of IR, NMR, and HRESIMS data, and verified by crystallography and degradative experiments. Compounds 1–7 represent the first reported instance of phenyl ribosides. The phytotoxic potency of the purified metabolites was assessed against seedlings of Chloris virgata and Portulaca oleracea. The results demonstrated that phenyl-O-β-d-ribofuranoside derivatives showed higher herbicidal activity than naphthalenones. Notably, compounds 1 and 2 demonstrated potent herbicidal activity against both weed species at 100 mg/L, exhibiting efficacy superior to the commercial herbicide glyphosate at the same concentration. Preliminary mechanism studies indicated that the phenyl-O-β-D-ribofuranoside derivatives probably exert their herbicidal effect by disrupting energy metabolism, specifically through the inhibition α-amylase functionality. These findings expand the structural diversity of phenolic glycosides and offer valuable leads for developing new fungal-derived herbicides.

Objective: Lanatoside C (Lan C), a cardiac glycoside, has demonstrated potent anti-cholangiocarcinoma activity. However, its potential cardiotoxicity at therapeutic doses remains poorly understood. This study aimed to systematically evaluate the cardiotoxicity of Lan C at cellular and organ levels and to elucidate its underlying molecular mechanisms. Methods: Human AC16 cardiomyocytes (ATCC® CRL-3568™) were employed for in vitro studies, with untreated cells included as negative controls. Cytotoxic effects at anti-cholangiocarcinoma-relevant concentrations (50–200 nM) were evaluated using a combination of cell viability assays, transmission electron microscopy, flow cytometry for apoptosis and reactive oxygen species (ROS) detection, JC-1 staining to assess mitochondrial membrane potential, lactate dehydrogenase (LDH) release assays, and Western blot analysis of apoptotic proteins. Male BALB/c mice were administered either vehicle (PBS) or Lan C (80 mg/kg/day) by oral gavage for 28 consecutive days. Cardiac function was assessed by echocardiography, and myocardial architecture was examined through histopathological analysis. Results: Lan C showed a dose-dependent inhibitory effect in vitro on AC16 cell viability and induced apoptosis. This process involved decreased mitochondrial membrane potential, increased reactive oxygen species (ROS), downregulation of the anti-apoptotic protein Bcl-2, and upregulation of cytochrome C, Cleaved Caspase-9, and Cleaved Caspase-3, indicating activation of the mitochondrial-dependent apoptotic pathway. In vivo , high-dose Lan C significantly impaired left ventricular systolic function, as indicated by reductions in LVEF and LVFS, and induced myocardial structural alterations. Conclusion: Lan C exhibits measurable but relatively low cardiotoxicity at concentrations effective against cholangiocarcinoma, with cardiac effects may be manageable at therapeutic doses. These findings support Lan C as a promising anti-tumor candidate with controllable cardiotoxicity under optimized dosing and clinical monitoring.

The rise of methicillin‐resistant Staphylococcus aureus (MRSA) and the ineffectiveness of current antibiotics make new treatments critically urgent. Fungi represent a promising source of anti‐MRSA drug leads. In this study, three new compounds, including (1 R ,3 S ,4 R ,10 R )‐3,4,10,11‐tetrahydroxybisabol‐7‐ene ( 1 ), 15 β ‐hydroxy methyl nortricycloalternarate ( 2 ), and 2,9 α ,10 β ,11 α ‐tetrahydroxy‐4‐methoxy‐13‐methyl‐9,10,11,12‐tetrahydro‐[6,8‐biphenyl]‐1‐carboxylic acid ( 5 ), along with 11 known compounds ( 3 , 4 , and 6 – 14 ) were isolated from the endophytic fungus Alternaria alternata LZU‐183. The structures of three new compounds were determined by a comprehensive analysis of the spectroscopic data. All 14 isolates were evaluated for their antibacterial activity against two strains of MRSA. Among them, the dibenzo‐ α ‐pyrones ( 5 – 9 , 11 – 12 , and 14 ) showed anti‐MRSA activity with MIC values ranging from 8.0 to 128.0 µg/mL. Compound 8 demonstrated the most potent activity, with MIC values of 8.0 and 16.0 µg/mL against the two MRSA strains, respectively.

Three new ent ‐atisane diterpenoids ( 1 − 3 ) and five known ones ( 4 − 8 ) were obtained from the bioactive fraction of E. micractina . Their structures and absolute configurations were elucidated by a comprehensive analysis of the spectroscopic data, including high‐resolution electrospray ionization mass spectrometry, infrared, nuclear magnetic resonance, X‐ray crystallography, and electronic circular dichroism data. Among them, compound 1 was the first example of an ent ‐atisane diterpenoid with an α ‐oriented hydroxyl group at C‐7. In addition, the cytotoxicity of all the isolated ent ‐atisane diterpenoids was evaluated against human cervical carcinoma, human acute promyelocytic leukemia, and human hepatoma cell lines. Compound 3 demonstrated significant cytotoxic activity against the selected cell lines with an IC ₅₀ value from 7.5 to 10.1 µM.

Phytochemical investigation on the anti‐inflammatory fraction extracted from the whole plant of Euphorbia helioscopia L. led to the isolation of three new ent‐atisane diterpenoids (1–3) and five known analogues (4–8). The structures and absolute configurations of the new compounds were elucidated by comprehensive analysis of the NMR, MS, IR, ECD, and X‐ray crystallography. It is worth mentioning that compound 3 belongs to a rare class of ent‐atisane diterpenoid featuring a hydroxyl group at C‐9. Bioactivity investigation showed that compounds 4, 7, and 8 exhibited significant inhibitory effects on LPS‐induced NO production in a dose‐dependent manner, which indicates their anti‐inflammatory potential.

Introduction: The incidence of cholangiocarcinoma (CCA) has increased worldwide in recent years. Given the poor prognosis associated with the current management approach of CCA, new therapeutic agents are warranted to improve the prognosis of this patient population.Methods: In this study, we extracted five cardiac glycosides (CGs) from natural plants: digoxin, lanatoside A, lanatoside C, lanatoside B, and gitoxin. Follow-up experiments were performed to assess the effect of these five extracts on cholangiocarcinoma cells and compounds with the best efficacy were selected. Lanatoside C (Lan C) was selected as the most potent natural extract for subsequent experiments. We explored the potential mechanism underlying the anticancer activity of Lan C on cholangiocarcinoma cells by flow cytometry, western blot, immunofluorescence, transcriptomics sequencing, network pharmacology and in vivo experiments.Results: We found that Lan C time-dependently inhibited the growth and induced apoptosis of HuCCT-1 and TFK-1 cholangiocarcinoma cells. Besides Lan C increased the reactive oxygen species (ROS) content in cholangiocarcinoma cells, decreased the mitochondrial membrane potential (MMP) and resulted in apoptosis. Besides, Lan C downregulated the protein expression of STAT3, leading to decreased expression of Bcl-2 and Bcl-xl, increased expression of Bax, activation of caspase-3, and initiation of apoptosis. N-acetyl-L-cysteine (NAC) pretreatment reversed the effect of Lan C. In vivo, we found that Lan C inhibited the growth of cholangiocarcinoma xenografts without toxic effects on normal cells. Tumor immunohistochemistry showed that nude mice transplanted with human cholangiocarcinoma cells treated with Lan C exhibited decreased STAT3 expression and increased caspase-9 and caspase-3 expression in tumors, consistent with the in vitro results.Conclusion: In summary, our results substantiates that cardiac glycosides have strong anti-CCA effects. Interestingly the biological activity of Lan C provides a new anticancer candidate for the treatment of cholangiocarcinoma.

Around 11% of all known gene lesions causing human genetic diseases are nonsense mutations that introduce a premature stop codon (PTC) into the protein-coding gene sequence. Drug-induced PTC readthrough is a promising therapeutic strategy for treating hereditary diseases caused by nonsense mutations. To date, it has been found that more than 50 small-molecular compounds can promote PTC readthrough, known as translational readthrough-inducing drugs (TRIDs), and can be divided into two major categories: aminoglycosides and non-aminoglycosides. This review summarizes the pharmacodynamics and clinical application potential of the main TRIDs discovered so far, especially some newly discovered TRIDs in the past decade. The discovery of these TRIDs brings hope for treating nonsense mutations in various genetic diseases. Further research is still needed to deeply understand the mechanism of eukaryotic cell termination and drug-induced PTC readthrough so that patients can achieve the greatest benefit from the various TRID treatments.

Two new azaphilones, penimultiones A and B, together with seven known analogs were isolated from the culture of Penicillium multicolor LZUC‐S2. Their structures were elucidated by detailed spectroscopic data analysis and chemical transformation. Penimultiones A and B belong to a rare class of azaphilones possessing a 1,3‐dioxolane moiety. In addition, all compounds were evaluated for their antibacterial activity against five clinically bacterial strains in vitro, and three compounds showed potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 12.5 to 50.0 μg/mL.