The Journal of Antibiotics

A new class of dimeric product isolated from the fungus Chaetomium globosum: evaluation of chemical structure and biological activity

Chaetomium globosum is a filamentous fungus from which we have previously isolated a series of interesting natural products. Here, we isolated a previously unknown natural product from the culture of C. globosum. Through spectroscopic and crystallographic characterization, we determined the compound to be a new dimerized azaphilone-type product which we termed cochliodone J (1). Furthermore, our investigation into the biological activity of the natural product determined that 1 was cytotoxic to human cervix carcinoma HeLa cells with an IC

TNF-α-induced down-regulation of type I interferon receptor contributes to acquired resistance of cervical squamous cancer to Cisplatin

We aimed to investigate the effects of tumor necrosis factor (TNF)-α on the expression of interferon α/β receptor subunit 1 (IFNAR1) and cervical squamous cancer (CSCC) resistance to Cisplatin, as well as the underlying mechanisms. Kaplan-Meier analysis was used to plot the overall survival curves. SiHa cells were treated with 20 ng/ml TNF-α to determine cell proliferation in human CSCC cells and the expression of IFNAR1. The effects of TNF-α on the downstream signaling pathway, including casein kinase 1α (CK1α), were investigated using the caspase protease inhibitor FK009, the c-Jun kinase inhibitor SP600125, and the nuclear factor kappa-B inhibitor ammonium pyrrolidinedithiocarbamate (PDTC). TNF-α induced down-regulation of IFNAR1 in human CSCC cells and promoted proliferation of SiHa cells. SiHa cells were transfected with the catalytic inactive mutant CK1α K49A, and the ability of TNF-α to induce down-regulation of IFNAR1 expression was found to be significantly diminished in this context. FK009 and PDTC had no obvious effect on the expression of CK1α, however, SP600125 significantly reduced the expression of CK1α in the presence of TNF-α. SiHa cells treated with TNF-α showed reduced sensitivity to Cisplatin and exhibited higher cell viability, while the sensitivity of SiHa cells to Cisplatin was restored after treatment with CK1α inhibitor D4476. Additionally, we constructed a TNF-α overexpressing SiHa cell line and a transplanted tumor model. The results were similar to those of in vitro efficacy. We demonstrate that TNF-α-induced down-regulation of type I interferon receptor contributes to acquired resistance of cervical squamous cancer to Cisplatin.

Diaporone A, a new antibacterial secondary metabolite from the plant endophytic fungus Diaporthe sp.

Diaporone A (1), one new dihydroisocoumarin derivative and four known α-dibenzopyrones, alternariol (2), 5'-hydroxyalternariol (3), alternariol 4,10-dimethyl ether (4), and alternariol 4-methyl ether (5) were isolated from the crude extract of the plant endophytic fungus Diaporthe sp. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as HRESIMS and comparison with data from the literature. The absolute configuration of 1 was assigned by electronic circular dichroism (ECD) calculations. Compound 1 showed moderate antibacterial activity against Bacillus subtilis with the MIC value of 66.7 μM, and exhibited weak cytotoxicity against human cervical carcinoma (HeLa) cell line with IC

Laxaphycins B5 and B6 from the cultured cyanobacterium UIC 10484

Two laxaphycin type-B cyclic dodecapeptides, laxaphycins B5 and B6, were obtained from UIC 10484, a freshwater cf. Phormidium sp. Analysis using the 16S rRNA sequence found UIC 10484 to clade with UIC 10045, a known laxaphycin type-A and -B producer, and MS/MS analysis revealed the presence of two novel laxaphycin type-B compounds. The structures of the metabolites were elucidated using 2D NMR and MS/MS. The absolute configurations of the amino acids were determined by advanced Marfey's analysis. Both metabolites were evaluated against the same three cancer cell lines. The IC