Polyketides, diketopiperazines and an isochromanone from the marine-derived fungal strain Fusarium graminearum FM1010 from Hawaii.

The fungal strain Fusarium graminearum FM1010 was isolated from a shallow-water volcanic rock known as "live rock" at the Richardson's Beach, Hilo, Hawaii. Eleven specialised metabolites, including two undescribed diketopiperazines, three undescribed polyketides, and one undescribed isochromanone, along with five known fusarielin derivatives were obtained from F. graminearum FM1010. The structures of the six undescribed compounds were elucidated by extensive analysis of NMR spectroscopy, HRESIMS, chemical reactions, and electronic circular dichroism (ECD) data. Kaneoheoic acids G-I showed mild inhibitory activity against S. aureus with the MIC values in the range of 20-40 µg/mL when assayed in combination with chloramphenicol (half of the MIC, 1 µg/mL), an FDA approved antibiotic. Kaneoheoic acid I exhibited both anti-proliferative activity against ovarian cancer cell line A2780 and TNF-α induced NF-κB inhibitory activity with the IC50 values of 18.52 and 15.86 µM, respectively.

Antibacterial kaneoheoic acids A-F from a Hawaiian fungus Fusarium sp. FM701.

Alarming rate of resistance to the existing antibiotics exhibits the importance of developing new antibiotic molecules from relatively under explored sources as well as implementing alternative approaches like antibiotic adjuvants. Six previously undescribed fungal polyketides, kaneoheoic acids A-F (1-6) were isolated from a fungal strain Fusarium sp. FM701 which was collected from a muddy sample of Hawaiian beach. The structures of these six compounds were elucidated by spectroscopic interpretation, including HRESIMS and NMR, and electronic circular dichroism (ECD) analysis. All six compounds that were inactive when tested alone showed significant antibacterial activity against Staphylococcus aureus and Bacillus subtilis, in the range of 10-80 µg/mL when assayed in combination with either chloramphenicol (half of the MIC, 1 µg/mL), an FDA approved antibiotic or disulfiram (6 µg/mL), an established antibiotic adjuvant that augmented the activity of antibiotics.