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Five new resorcylic acid lactones (RALs) hispidulactones A-E (1, 4, 5, 8, and 9), a new natural product (2), and four known ones (3, 6, 7, and 10) with different ring systems were isolated from the desert plant endophytic fungus Chaetosphaeronema hispidulur. The new compounds were characterized by NMR data, CD spectra, and X-ray experiment. The new natural product (2) displayed strongly biological effects on the seedlings growth of Arabidopsis thaliana, Digitaria sanguinalis, and Echinochloa crusgalli with a dose-dependent relationship. Compounds 1, 2, and 6 were also tested cytotoxic activities against three cancer cell lines HCT116, Hela, and MCF7 and only did the new natural product (2) display biological activities with IC50 values at 54.86 +/- 1.52, 4.90 +/- 0.02, and 20.04 +/- 4.00 mu M, respectively, whereas the IC50 values of the positive control cis-platinum were 11.36 +/- 0.42, 3.54 +/- 0.12, and 14.32 +/- 1.01 mu M, respectively.