A novel depsipeptide (PM181110) was purified from an endophytic fungus Phomopsis glabrae isolated from the leaves of Pongamia pinnata (family Fabaceae). The chemical structure of PM181110 was ...elucidated using physiochemical properties, 2D NMR and other spectroscopic methods. PM181110 is very close in structure to FE399. The compound exhibited in vitro anticancer activity against 40 human cancer cell lines with a mean IC50 value of 0.089 μM and ex vivo efficacy towards 24 human tumor xenografts (mean IC50=0.245 μM).
Puffy hand syndrome is a complication of intravenous drug misuse. Users themselves are often aware of the risk, particularly from hand injections, but most physicians, including addiction specialists ...and general practitioners, rarely encounter this presentation and might not be familiar with it.
2,5-bis(3'-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited ...concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.
Three new 22-membered macrolactone antibiotics, atacamycins A-C, were produced by Streptomyces sp. C38, a strain isolated from a hyper-arid soil collected from the Atacama Desert in the north of ...Chile. The metabolites were discovered in our HPLC-diode array screening and isolated from the mycelium by extraction and chromatographic purification steps. The structures were determined by mass spectrometry and NMR experiments. Atacamycins A, B and C exhibited moderate inhibitory activities against the enzyme phosphodiesterase (PDE-4B2), whereas atacamycin A showed a moderate antiproliferative activity against adeno carcinoma and breast carcinoma cells.
Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still disease (AOSD). Herein we report on the ...effectiveness of anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD.
This is a multicenter study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers.
The cumulative retention rate of ANA at 12-, 24-, 48-, and 60-month of follow-up was 74.3%, 62.9%, 49.4%, and 49.4%, respectively, without any significant differences between sJIA and AOSD patients (
= 0.164), and between patients treated in monotherapy compared with the subgroup coadministered with conventional disease-modifying antirheumatic drugs (cDMARDs) (
= 0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (
= 0.009), which persisted even after adjustment for pathology (
= 0.013). In the regression analysis, patients experiencing adverse events (AEs) {hazards ratio (HR) = 3.029 confidence interval (CI) 1.750-5.242,
< 0.0001} and those previously treated with other biologic agents HR = 1.818 (CI 1.007-3.282),
= 0.047 were associated with a higher HR of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (
< 0.0001). Significant corticosteroid-sparing (
= 0.033) and cDMARD-sparing effects (
< 0.0001) were also recorded. Less than one-third of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin.
Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient's safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant drug-sparing effect and showed an overall good safety profile.
Five new congeners of elaiomycin featuring the rare azoxy function were isolated from Streptomyces sp. strain HKI0708. Individual elaiomycins exhibit specific antimycobacterial, anti-Aspergillus, and ...cytotoxic activities, providing provisional data on structure–activity relationships. The co-occurrence of the azoxide variants indicates a biogenetic relationship that illustrates new diversification steps in elaiomycin biosynthesis.
Histone deacetylase inhibitors are a group of recently developed compounds that modulate cell growth and survival. We evaluated the effects of the histone deacetylase inhibitor MGCD0103 on growth of ...pancreatic carcinoma models following single agent treatment and in combination with gemcitabine. MGCD0103 inhibited tumor cell growth and acted synergistically with gemcitabine to enhance its cytotoxic effects. Gene expression analysis identified the cell cycle pathway as one of the most highly modulated gene groups. Our data suggest that MGCD0103 + gemcitabine might be an effective treatment for gemcitabine‐refractory pancreatic cancer. (Cancer Sci 2011; 102: 1201–1207)
Epoxyphomalins A (1) and B (2) are highly potent cytotoxic fungal metabolites. During the course of purifying larger quantities of 1 and 2 from Paraconiothyrium sp. fermentation extracts, three new ...epoxyphomalins (3−5) were isolated and characterized, showing modifications to the oxidation pattern of the cyclohexene moiety or of C-9 of the decalin system. IC50 values for cytotoxicity against a panel of 36 human tumor cell lines were determined for all new compounds. Compound 4 was found to be cytotoxic particularly toward prostate PC3M (IC50 = 0.72 μM) and bladder BXF 1218 L (IC50 = 1.43 μM) cancer cell lines. In addition, inhibition of chymotrypsin-, caspase-, and trypsin-like activity of purified 20S proteasomes was determined for epoxyphomalins A (1) and B (2). The results indicate that compounds 1 and 2 exert their cytotoxic effect through potent inhibition of the 20S proteasome.
The ethyl acetate extract from the Streptomyces sp. isolate B8652 delivered the trioxacarcins A-C (2a-2c) and additionally three new derivatives designated as trioxacarcins D-F (2d-2f). All ...trioxacarcins showed high anti-bacterial and some of them high anti-tumor and anti-malaria activity. The structures of the new antibiotics were derived from mass, 1D and 2D NMR spectra and confirmed by comparison of the NMR data with those of known derivatives. The absolute configuration of the trioxacarcins is deduced from the X-ray analysis of gutingimycin (2g) and from the known stereochemistry of the L-trioxacarcinoses A and B.
Investigation of the fungal strain Monodictys putredinis isolated from the inner tissue of a marine green alga led to the isolation of four new monomeric xanthones and a benzophenone. All structures ...were elucidated by extensive spectroscopic measurements. The relative configuration of compound 1 was determined by X-ray crystal structure analysis, while for 2 and 3 configurations were confirmed by NOE experiments. Absolute configurations for compounds 1−3 were deduced by comparing experimental circular dichroism spectroscopic data with those calculated employing quantum-chemical time-dependent density functional theory (TDDFT). The compounds were examined for their cancer chemopreventive potential. Xanthone 2 was shown to inhibit cytochrome P450 1A activity with an IC50 value of 3.0 μM. Compounds 2 and 3 displayed moderate activity as inducers of NAD(P)H:quinone reductase (QR) in cultured mouse Hepa 1c1c7 cells, with CD values (concentration required to double the specific activity of QR) of 12.0 and 12.8 μM, respectively. Compound 3 showed weak inhibition of aromatase activity.
PDF
