Abstract
Coculture fermentation of Penicillium fuscum and P. camembertii/clavigerum yielded berkeleypenostatins A-G (1-7) as well as the previously reported berkeleylactones A-H, the known macrolide A26771B, citrinin, and patulin. As was true with the berkeleylactones, there was no evidence of the berkeleypenostatins in either axenic culture. The structures were deduced from analyses of spectral data, and the absolute configuration of berkeleypenostatin A (1) was determined by single-crystal X-ray crystallography. Berkeleypenostatins A (1) and E (5) inhibited migration of human pancreatic carcinoma cells (HPAF-II). Both compounds were tested by the NCI Developmental Therapeutics Program. In the NCI 60 cell five-dose screen, berkeleypenostatin E (5) was the more active of the two, with 1-10 μM total growth inhibition (TGI) of all leukemia cell lines, as well as the majority of colon, CNS, melanoma, ovarian, prostate, renal, and breast cancer cell lines.
| Original language | English |
|---|---|
| Pages (from-to) | 1656-1665 |
| Number of pages | 10 |
| Journal | Journal of Natural Products |
| Volume | 84 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 28 2021 |
Funding
We thank NIH for the grants that supported this research: 1R15AI131161-01A1, P20GM103546, and 5P30NS055022. We also thank NSF grant #CHE-9977213 for acquisition of an NMR spectrometer and the M. J. Murdock Charitable Trust Reference #2015427:JAT:2/25/2016 for support of Apedaile’s work and ref #99009:JVZ:11/18/99 for acquisition of the mass spectrometer. The Macromolecular X-ray Diffraction Core Facility at the University of Montana was supported by a Centers of Biomedical Research Excellence grant from the National Institute of General Medical Sciences (P20GM103546) and by the National Science Foundation (NSF)-MRI (CHE-1337908).
| Funder number |
|---|
| JAT:2/25/2016, 99009, JVZ:11/18/99, -9977213, 2015427, 5P30NS055022 |
| P20GM103546 |
| R15AI131161 |
| CHE-1337908 |
