Hybrid Polyketides from a Hydractinia-Associated Cladosporium sphaerospermum SW67 and Their Putative Biosynthetic Origin.
Five hybrid polyketides (1a, 1b, and 2-4) containing tetramic acid core including a new hybrid polyketide, cladosin L (1), were isolated from the marine fungus Cladosporium sphaerospermum SW67, which was isolated from the marine hydroid polyp of Hydractinia echinata. The hybrid polyketides were isolated as a pair of interconverting geometric isomers. The structure of 1 was determined based on 1D and 2D NMR spectroscopic and HR-ESIMS analyses. Its absolute configuration was established by quantum chemical electronic circular dichroism (ECD) calculations and modified Mosher's method. Tetramic acid-containing compounds are reported to be derived from a hybrid PKS-NRPS, which was also proved by analyzing our 13C-labeling data. We investigated whether compounds 1-4 could prevent cell damage induced by cisplatin, a platinum-based anticancer drug, in LLC-PK1 cells. Co-treatment with 2 and 3 ameliorated the damage of LLC-PK1 cells induced by 25 μM of cisplatin. In particular, the effect of compound 2 at 100 μM (cell viability, 90.68 ± 0.81%) was similar to the recovered cell viability of 88.23 ± 0.25% with 500 μM N-acetylcysteine (NAC), a positive control.
['Lee|Seoung Rak|SR|', 'Lee|Dahae|D|', 'Eom|Hee Jeong|HJ|', 'Rischer|Maja|M|', 'Ko|Yoon-Joo|YJ|', 'Kang|Ki Sung|KS|', 'Kim|Chung Sub|CS|0000-0001-9961-4093', 'Beemelmanns|Christine|C|0000-0002-9747-3423', 'Kim|Ki Hyun|KH|0000-0002-5285-9138']
D000818:Animals D000970:Antineoplastic Agents D002470:Cell Survival D002945:Cisplatin D002963:Cladosporium D018374:LLC-PK1 Cells D015394:Molecular Structure D019906:Nuclear Magnetic Resonance, Biomolecular D010802:Phylogeny D061065:Polyketides D011760:Pyrrolidinones D013552:Swine
hybrid polyketides Cladosporium sphaerospermum tetramic acid hybrid PKS-NRPS LLC-PK1 cells