Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives bearing dithiocarbamate chains / 药学学报

A series of 4(3H)-quinazolinone derivatives bearing dithiocarbamate side chains have been synthesized through the reaction of 6-bromomethyl-2-methyl-4(3H)-quinazolinone with CS2 and various amines in the presence of anhydrous K3PO4, and their structures were confirmed with ESI-MS, H NMR, elemental analysis or HRMS. The target compounds 8a -8q were tested for their in vitro antitumor activity against human myelogenous leukaemia K562 and human Hela cell lines by means of colorimetric MTT assay. Among the tested compounds, 8q exhibited in vitro inhibitory activity against K562 and Hela cells with IC50 values of 0.5 and 12.0 micromol x L(-01), respectively. Therefore, compound 8q is worthy to be a lead compound for the design and synthesis of new antitumor agents.

Effects of budesonide on chronic airway inflammation in guinea pigs sensitized with repeated exposure to allergen / 中华儿科杂志

<p><b>OBJECTIVE</b>Inhaled glucocorticosteroids (ICS) remains the first line controller medication for chronic airway inflammation in asthma till now. If the impact of allergen could not be eliminated, how would the improvement of airway inflammation be achieved with inhaled glucocorticosteroids therapy? What was its effect on airway remodeling? In this study, an animal model of asthma was established and the effects of budesonide on airway allergic inflammation and extracellular matrix (ECM) deposition in sensitized guinea pigs with repeated exposure to allergen were investigated.</p><p><b>METHODS</b>Thirty-two male Hartley guinea pigs were randomly divided into four groups with 8 in each group: (A) Group of repeated exposure to ovalbumin (OVA), (B) Group of repeated exposure to OVA plus budesonide (BUD) intervention, (C) Group of stopping repeated exposure to OVA plus stopping BUD intervention, (D) Control group. At 24 h after the last OVA challenge (8 weeks after the first OVA challenge), bronchoalveolar lavage fluid (BALF) was collected from each animal. Total and differential leukocyte counts in BALF was performed on cell suspension smear stained with May-Grünwald-Giemsa (MGG) method. The upper lobe of right lung was removed and regularly fixed, then paraffin embedded lung tissues sections were prepared. The count of eosinophils infiltrated in the airway wall was performed on H&E stained lung tissue sections with LEICA Q500IW computerized image analysis system. Fibronectin and collagen type III (Col-III) deposited in the airway wall were detected by immunohistochemical staining on the paraffin embedded lung tissues sections. The intensity of positive reaction of fibronectin or Col-III deposited in the airway wall was analyzed with LEICA Q500IW computerized image analysis system.</p><p><b>RESULTS</b>The count of eosinophils in BALF (x 10(5)/ml) of group A and B were higher than that of group C and D (35.70 +/- 25.22, 11.49 +/- 5.51 vs. 1.00 +/- 0.90, 1.02 +/- 0.78, P < 0.01), the difference between group A and B, group B and C was significant. The count of eosinophils infiltrated at each level of airway wall in group A and B were higher than that of group C and D (large airway: 6.95 +/- 2.28, 1.54 +/- 1.09 vs. 0.76 +/- 0.45, 0.88 +/- 0.25; medial airway: 9.22 +/- 3.89, 3.99 +/- 2.3 vs. 1.25 +/- 1.20, 0.64 +/- 0.36; small airway: 11.56 +/- 4.02, 2.67 +/- 1.15 vs. 1.32 +/- 0.83, 0.43 +/- 0.24, P < 0.01), the difference between group A and B, group B and C was significant. The gray values of fibronectin deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 122 +/- 22, 174 +/- 23 vs. 219 +/- 34, 229 +/- 20; small airway 135 +/- 29, 165 +/- 41 vs. 236 +/- 20, 220 +/- 16, P < 0.05), the difference between group A and B, group B and C was significant. The gray values of Col-III deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 153 +/- 21, 174 +/- 22 vs. 189 +/- 14, 200 +/- 18; small airway 133 +/- 23, 176 +/- 20 vs. 191 +/- 14, 198 +/- 20, P < 0.05), the difference between group A and B was significant.</p><p><b>CONCLUSION</b>Inhaled budesonide could partially inhibit allergic inflammation and ECM deposition in airway wall in guinea pig chronic asthma model with repeated exposure to allergen. Early inhaled budesonide combined with avoidance of OVA exposure could completely inhibit allergic inflammation and ECM deposition. These results suggest that the inhibitory effect on airway allergic inflammation and airway remodeling of inhaled glucocorticosteroids would be limited when the allergen factor could not be avoided.</p>

Relationship between bronchial hyperresponsiveness and the peripheral obstruction in stable asthmatic children / 中华儿科杂志

<p><b>OBJECTIVE</b>Asthma is the most common chronic respiratory disease of children. The association between asthma and bronchial hyperresponsiveness (BHR) has been well-demonstrated. The objective of the study was to investigate relationship between the bronchial responsiveness and the peripheral obstruction in stable asthmatic children.</p><p><b>METHODS</b>Thirty-nine children with stable asthma, 28 boys and 11 girls with a mean age of 128 (77 - 197) months, received the bronchial provocation test by the maximal expiratory flow-volume (MEFV) curve measurement. The children were divided into two groups: one with maximal mid-expiratory flow (MMEF) < 80% (n = 15) and the other with MMEF >/= 80% (n = 24). Positive rates of bronchial provocation test were compared between groups of MMEF < 80% and >/= 80% and between the children whose relief duration was </= 12 months (n = 26) and > 12 months (n = 13). Statistical analysis was performed by using Chi-square, rank sum test or t test (SPSS10.0), P values < 0.05 were considered significant.</p><p><b>RESULTS</b>In the 39 stable asthmatic children, 15 (38%) were detected MMEF < 80% and 28 (72%) had BHR. There was no significant difference in BHR between the children with MMEF < 80% and those with MMEF >/= 80% (P > 0.05). There was no significant difference in BHR between the children whose relief duration was </= 12 months and > 12 months (P > 0.05), either.</p><p><b>CONCLUSIONS</b>The stable asthmatic children still had peripheral obstruction and BHR, which indicated the presence of airway inflammation. There was no significant difference in BHR between the children whose relief duration was </= 12 months and > 12 months.</p>