2-Amino-3-cyano-4-(5-arylisoxazol-3-yl)-4H-chromenes: synthesis and in vitro cytotoxic activity

A new series of 4-aryl-4H-chromenes bearing a 5-arylisoxazol-3-yl moiety at the C-4 position were prepared as potential anticancer agents. The in vitro cytotoxic activity of the synthesized compounds was investigated against a panel of tumor cell lines including MCF-7 (breast cancer), KB (nasopharyngeal epidermoid carcinoma), Hep-G2 (liver carcinoma), MDA-MB-231 (breast cancer), and SKNMC (human neuroblastoma) using the MTT colorimetric assay. Doxorubicin, a well-known anticancer drug, was used as positive standard drug. Among the synthesized compounds, the 5-(3-methylphenyl)isoxazol-3-yl analog (7j) showed the most potent cytotoxic activity against all five human tumor cell lines.     

Epidemic methicillin-susceptible Staphylococcus aureus lineages are the main cause of infections at an Iranian university hospital

The majority of Staphylococcus aureus infections from Isfahan, Iran, were caused by epidemic methicillin-susceptible S. aureus (MSSA) lineages, sequence type 8 (ST8), ST22, ST30, and ST6. The predominant methicillin-resistant S. aureus strain was ST239. We observed a high prevalence of Panton-Valentine leukocidin-positive MSSA strains (19.7%), which is a matter of considerable concern, since these strains have the ability to cause severe infections.     

Thieno[2,3-b]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease

In search of safer tacrine analogs, various thieno[2,3-b]pyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC₅₀ values of 1.55 and 0.23 µM, respectively. The most active ChE inhibitors ( 5e and 5d ) were also candidates for further complementary assays, such as kinetic and molecular docking studies as well as studies on inhibitory activity towards amyloid-beta (βA) aggregation and β-secretase 1, neuroprotectivity, and cytotoxicity against HepG2 cells. Our results indicated efficient anti-Alzheimer's activity of the synthesized compounds.     

The Flavone Luteolin Improves Central Nervous System Disorders by Different Mechanisms: A Review

The aim of our study is to build a framework for a better understanding of high-grade glioma (HGG) prognostic-related biomarkers. Whole-genome gene expression microarray was performed to identify differently expressed genes between HGGs and low-grade diffuse gliomas. Several machine learning algorithms were used to filter prognostic-related genes. One hundred ninety-three HGG patients after surgical resection were selected for survival analysis. Immunohistochemistry were performed on these tumor samples to analyze IDH1 mutation status and protein expression of WEE1. qRT-PCR, western blotting, transwell assays, and scratch wound healing assays were performed to evaluate the effect of WEE1 knockdown or overexpression in HGG cells. Three prognostic-related genes (WEE1, IGF2PB3, and EMP3) were demonstrated to separate HGG patients into two different survival subgroups. The area under receiver operating characteristic curve of WEE1 was higher than that of IGF2BP3, EMP3, age, IDH status, 1p/19q status, and MGMT promoter status. WEE1 was an independent covariate compared with IDH status, age, and WHO grade. Knockdown or overexpression of WEE1 can inhibit or promote migration and invasion in U251 and U87 cell lines. WEE1, EMP3, and IGF2BP3 are reliable prognostic-related genes at the mRNA level. WEE1 is an independent prognostic biomarker in survival analysis and has potential diagnostic value for HGG patients. WEE1 can induce HGG cell migration and invasion in vitro.     

Anticoagulant activity of isolated coumarins (suberosin and suberenol) and toxicity evaluation of Ferulago carduchorum in rats

Context: Ferulago carduchorum Boiss. &; Hausskn. (Apiaceae) is known as Chavil in Persian which grows in west of Iran. Local people add Chavil to dairy and oil ghee as a natural preservative to extend the expiration date.

Objective: The goal of this survey is the safety evaluation of the total extract of F. carduchorum in rats by determining both oral acute and subchronic toxicities; furthermore, the anticoagulant activity of isolated coumarins was evaluated.

Materials and methods: The aerial parts of F. carduchorum were extracted by the percolation method. The anticoagulant activity of isolated coumarins was evaluated and the total extract was used to investigate acute and subchronic toxicity in rats. In the subchronic toxicity model, doses of 250, 500, and 1000?mg/kg of the extract were administered to treated groups for 30?consecutive days by gavage.

Results: According to the results of acute toxicity, the LD₅₀ of Chavil extract was more than 2000?mg/kg. The subchronic study showed no significant difference (p?>?0.05) between the groups treated with extract and control groups in hematological (erythrocyte, total and differential leukocyte, hematocrit, hemoglobin, platelet count) and biochemical parameter (glucose, albumin, cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) evaluations. The isolated coumarins (suberosin and suberenol) prolonged the prothrombin time (PT) at doses of 3 and 6?mg/kg compared with control (p?Conclusion: In conclusion, oral administration of the Chavil extract did not cause either acute or subchronic toxicities although the coumarins showed anticoagulant effect in rats.     

In vitro antimicrobial and acetylcholinesterase inhibitory activities of coumarins from <Emphasis Type="Italic">Ferulago</Emphasis><Emphasis Type="Italic">carduchorum</Emphasis>

Ferulago carduchorum (Apiaceae) is an endemic plant of Iran. From the hexane and ethyl acetate extracts of F. carduchorum seven coumarins, one flavonoid and one steroid were isolated using column chromatography with silica gel and Sephadex LH₂₀ as the stationary phases. Antimicrobial activity of the isolated compounds was examined by a broth microdilution method. Acetylcholinesterase (AChE) inhibitory activity of isolated coumarins was also investigated. The isolated compounds were identified as suberosin, suberenol, bergapten, xanthotoxin, isopimpinellin, prantschimgin, β-sitosterol and hesperetin by comparison of their NMR and MS spectral data with those reported in the literature. Evaluation of the minimum inhibitory concentration (MIC) for each compound showed that hesperetin (flavonoid) was the most potent antimicrobial agent against a gram-positive bacterium (Staphylococcus aureus) and among the coumarins, bergapten had the best activity against S. aureus and Candida albicans. All coumarins inhibited AchE enzyme, in which xanthotoxin showed the most inhibitory among them (IC₅₀ = 39.64 µM). Our results indicate that isolated coumarins are effective against the tested bacterial strains and have AchE inhibitory activity suggesting their potential for commercial applications.