Kwanruthai Tadpetch

Tetrahydroanthraquinone and xanthone derivatives from the marine-derived fungus Trichoderma aureoviride PSU-F95

Trichodermaquinone (1) and trichodermaxanthone (2) were isolated from the marine-derived fungus Trichoderma aureoviride PSU-F95 together with eleven known compounds. The structures were interpreted by spectroscopic methods. Known coniothranthraquinone 1 and emodin displayed strong antibacterial activity against methicillin-resistant Staphylococcus aureus with the MIC values of 8 and 4 μg/mL, respectively.

Penicillanthone and penicillidic acids A–C from the soil-derived fungus Penicillium aculeatum PSU-RSPG105

A new xanthone (penicillanthone, 1) and three new diphenyl ether derivatives (penicillidic acids A–C, 2–4) together with 14 known compounds (5–18) were isolated from the soil-derived fungus Penicillium aculeatum PSU-RSPG105. The structures were elucidated by spectroscopic analyses. The absolute configuration of compound 1 was determined using the Snatzkes method whereas those of compounds 2–4 was established by comparison of their optical rotations with those of structurally related compounds. Compound 5 exhibited mild antimycobacterial activity against Mycobacterium tuberculosis with an MIC value of 25 μg mL−1 and was noncytotoxic to noncancerous Vero cells. In addition, altenusin (12) displayed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus with an MIC value of 32 μg mL−1 and mild activity towards Vero cells with an IC50 value of 19.46 μM.

A fungal metabolite zearalenone as a CFTR inhibitor and potential therapy of secretory diarrheas

Graphical abstract Figure. No Caption available. Abstract Overstimulation of CFTR‐mediated Cl− secretion plays an important role in the pathogenesis of secretory diarrheas, which remain an important global health problem. This study aimed to identify inhibitors of CFTR‐mediated Cl− secretion from a library of fungus‐derived compounds and to evaluate their pharmacological properties and anti‐diarrheal utility. We identified zearalenone, 7′‐dehydrozearalenone and 8′‐hydroxyzearalenone isolated from the seagrass‐derived fungus Fusarium sp. PSU‐ES123 as inhibitors of CFTR‐mediated Cl− secretion in human intestinal epithelial (T84) cells. Being the most potent fungal metabolite capable of inhibiting CFTR‐mediated Cl− secretion, zearalenone reversibly inhibited CFTR Cl− channel activity in T84 cells with an IC50 of ˜0.5 &mgr;M. Functional and biochemical analyses and molecular docking studies indicate that zearalenone binds to the &bgr;‐estradiol binding sites in the ATP‐binding pockets on NBD1 and NBD2 of CFTR. Mechanisms of CFTR inhibition by zearalenone do not involve activation of phosphodiesterases, protein phosphatases, multidrug‐resistance protein 4 and AMP‐activated protein kinases. Importantly, zearalenone significantly inhibited cholera toxin (CT)‐induced Cl− secretion in T84 cells and blocked CT‐induced intestinal fluid secretion in mice. Collectively, our study indicates that zearalenone represents the first class of fungus‐derived CFTR inhibitors. Further development of this class of compounds may provide an effective treatment of secretory diarrheas.