Trichoderone, a novel cytotoxic cyclopentenone and cholesta-7, 22-diene-3 beta, 5 alpha, 6 beta-triol, with new activities from the marine-derived fungus Trichoderma sp.
The historical paradigm of the deep ocean as a biological 'desert' has shifted to one of a 'rainforest' owing to the isolation of many novel microbes and their associated bioactive compounds. To explore the potential of the bioactive compounds in our marine microbial natural product library, we screened it for the selective cytotoxicity of six different cancer cell lines to human normal lung fibroblast cell line HLF. The crude extract from a marine-derived fungal strain showed notable selectivity against cancer cell lines. For a bioactivity-guided fractionation and purification, a novel cyclopentenone, (-)-(4R *, 5S *)-3-ethyl-4,5-dihydroxycyclopent-2-enone (1, trichoderone), and a known compound with new activity, cholesta-7,22- diene-3 beta,5 alpha,6 beta-triol (2), were identified from a marine Trichoderma sp. that was isolated from the deep sea sediment of the South China Sea. Their structures were determined by NMR and MS data analyses. Trichoderone (1) displayed potent cytotoxicity against a panel of six cancer cell lines, whereas it did not show much cytotoxicity against normal human lung fibroblast cell line HLF even at a concentration of 7.02 mM. The selectivity index (SI) value for 1 was greater than 100. To the best of our knowledge, both compounds were isolated from marine fungi for the first time. They also exhibited bioactivities against HIV protease and Taq DNA polymerase. Optimization of the compounds would shed new light on treating cancer and infectious diseases.
You
Jianlan
J
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 510663 Guangzhou, People's Republic of China.
Dai
Huanqin
H
Chen
Zhihui
Z
Liu
Guangjie
G
He
Zhengxiang
Z
Song
Fuhang
F
Yang
Xiang
X
Fu
Haian
H
Zhang
Lixin
L
Chen
Xiaoping
X
D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002681:China; D003517:Cyclopentanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019015:Geologic Sediments / Q000382:microbiology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014242:Trichoderma / Q000737:chemistry* / Q000302:isolation & purification
D000970:Antineoplastic Agents; D003517:Cyclopentanes; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; C013905:cyclopentenone