| In vitro: |
| Nat Prod Res. 2017 Aug;31(16):1958-1962. | | Antituberculosis compounds from a deep-sea-derived fungus Aspergillus sp. SCSIO Ind09F01.[Pubmed: 28068839 ] | Eleven diketopiperazine and fumiquinazoline alkaloids (1-11) together with a tetracyclic triterpenoid helvolic acid (12) were obtained from the cultures of a deep-sea derived fungus Aspergillus sp. SCSIO Ind09F01.
METHODS AND RESULTS:
The structures of these compounds (1-12) were determined mainly by the extensive NMR, ESIMS spectra data and by comparison with previously described compounds. Besides, anti-tuberculosis, cytotoxic, antibacterial, COX-2 inhibitory and antiviral activities of these compounds were evaluated.
CONCLUSIONS:
Gliotoxin (3), 12,13-dihydroxy-fumitremorgin C (11) and helvolic acid (12) exhibited very strong anti-tuberculosis activity towards Mycobacterium tuberculosis with the prominent MIC50 values of <0.03, 2.41 and 0.894 μM, respectively, which was here reported for the first time. Meanwhile gliotoxin also displayed significant selective cytotoxicities against K562, A549 and Huh-7 cell lines with the IC50 values of 0.191, 0.015 and 95.4 μM, respectively. | | Front Pharmacol. 2017 Jul 7;8:319. | | Gliotoxin Targets Nuclear NOTCH2 in Human Solid Tumor Derived Cell Lines In Vitro and Inhibits Melanoma Growth in Xenograft Mouse Model.[Pubmed: 28736522 ] |
METHODS AND RESULTS:
The effect of Gliotoxin on cell viability and its clinical relevance was evaluated in vitro and in a melanoma xenograft mouse model. Cell lines derived from melanoma (518A2), hepatocellular carcinoma (SNU398, HCC-3, Hep3B), and pancreas carcinoma (PANC1) express high amounts of nuclear NOTCH2. Gliotoxin efficiently induced apoptosis in these cell lines whereas the GSI DAPT was ineffective. The specificity of Gliotoxin was demonstrated in the well differentiated nuclear NOTCH negative cell line Huh7, which was resistant to Gliotoxin treatment in vitro. In xenotransplanted 518A2 melanomas, a single day dosing schedule of Gliotoxin was well tolerated without any study limiting side effects. Gliotoxin significantly reduced the tumor volume in early (83 mm3 vs. 115 mm3, p = 0.008) as well as in late stage (218 mm3 vs. 576 mm3, p = 0.005) tumor models.
CONCLUSIONS:
In conclusion, NOTCH2 appears to be a key target of Gliotoxin in human neoplasias and Gliotoxin deserves further evaluation as a potential therapeutic agent in cancer management. |
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