The fungi of the genus Aspergillus are an important source of prenylated indole alkaloids,1 which showed a wide spectrum of biological activity, for example, antifungal,2 cytotoxic,3 and insecticidal4 activities. As part of our research program on the utilization of soil fungi, we investigated secondary metabolites produced by Aspergillus sp. PSU-RSPG185 isolated from soil collected from the Plant Genetic Conservation Project under the Royal Initiation of Her Royal Highness Princess Maha Chakri Sirindhorn at Ratchaprapa Dam in Suratthani province, Thailand. The crude EtOAc extract from the mycelia of the fungus PSU-RSPG185 was subjected to various chromatographic techniques leading to the isolation of six new indole-benzodiazepinedione derivatives, asperdiazapinones AeF (1e6), together with (2S,3R,11S)-aszonalenin (7),5 fumitremorgin C (8),6 and an N-prenyl derivative of fumitremorgin C (9).7 Some of the isolated compounds were evaluated for antimalarial (against Plasmodium falciparum, K1 multidrug resistant strain), and cytotoxic activity against noncancerous Vero (African green monkey kidney fibroblasts), MCF7 (human breast cancer), and KB (human oral cavity cancer) cells. This is the first report on the isolation of 7, an enantiomer of the natural (2R,3S,11R)-aszonalenin, and 9 as natural products.