作者: Arakawa, Emi ; Hirose, Tomoyasu ; Watanabe, Yoshihiro ; Iwatsuki, Masato ; Kondo, Naozumi ; Sunazuka, Toshiaki ; Nonaka, Kenichi ; Hokari, Rei ; Ikeda, Akari ; Ishiyama, Aki

Two new antimalarial compounds, named deacetyl fusarochromene (1) and 4'-O-acetyl fusarochromanone (2), were discovered from the static fungal cultured material of Fusarium sp. FKI-9521 isolated from feces of a stick insect (Ramulus mikado) together with three known compounds fusarochromanone (3), 3'-N-acetyl fusarochromanone (4), and 5 (fusarochromene or banchromene). The structures of 1 and 2 were elucidated as new analogs of 3 by MS and NMR analyses. The absolute configurations of 1, 2, and 4 were determined by chemical derivatization. All five compounds showed moderate in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with IC₅₀ values ranging from 0.08 to 6.35 µM.

2015-12-08·Oncotarget

Fusarochromanone-induced reactive oxygen species results in activation of JNK cascade and cell death by inhibiting protein phosphatases 2A and 5

Article

作者: Chen, Xin ; Salvatore, Brian A. ; Shang, Chaowei ; Jiang, Shanxiang ; Barzegar, Mansoureh ; Wu, Yang ; Huang, Shile ; Gu, Ying ; Mahdavian, Elahe

Recent studies have shown that fusarochromanone (FC101), a mycotoxin, is cytotoxic in a variety of cell lines. However, the molecular mechanism underlying its cytotoxicity remains elusive. Here we found that FC101 induced cell death in COS7 and HEK293 cells in part by activating JNK pathway. This is evidenced by the findings that inhibition of JNK with SP600125 or expression of dominant negative c-Jun partially prevented FC101-induced cell death. Furthermore, we observed that FC101-activated JNK pathway was attributed to induction of reactive oxygen species (ROS). Pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger and antioxidant, suppressed FC101-induced activation of JNK and cell death. Moreover, we noticed that FC101 inhibited the serine/threonine protein phosphatases 2A (PP2A) and 5 (PP5) in the cells, which was abrogated by NAC. Overexpression of PP2A or PP5 partially prevented FC101-induced activation of JNK and cell death. The results indicate that FC101-induced ROS inhibits PP2A and PP5, leading to activation of JNK pathway and consequently resulting in cell death.

2014-12-01·BMC Research Notes

Biological activities of fusarochromanone: a potent anti-cancer agent

Article

作者: Christopher G. Kevil ; Tara Williams-Hart ; Brian A. Salvatore ; Ying Gu ; Gopi K. Kolluru ; Yong-Yu Liu ; Phillip Palyok ; Mansoureh Barzegar ; Shile Huang ; Elahe Mahdavian ; Steven Adelmund ; John L. Clifford ; Kaustubh N. Bhinge ; Yang Wu ; Yoon-Jee Kim ; Quincy A. Quick ; Brian D. Furmanski

BACKGROUNDFusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity.RESULTSHerein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells.CONCLUSIONSOur data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101's molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.

100 项与 FC101 相关的药物交易

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