AIMA series of substituted phenyliminomethylenecoumarins derivatives was designed in order to find compounds possessing anticancer activities.

METHODSTitle compounds (1a-b, 2a-b and 3a-q) were synthesized and screened by several anticancer models in vitro.

RESULTSTwenty-one new compounds (1a-b, 2a-b and 3a-q) were synthesized and screened. Structures of the new compunds were determined by MS, HNMR and elemental analysis. Twelve compounds (3c, 3d, 3e, 3f, 3g, 3h, 3j, 3k, 3m, 3o, 3p, 3q) showed inhibitory effects on HCT-8, KB and Bel7402 cell lines in vitro.

CONCLUSIONSome compounds had certain anticancer activities and were worth further studying.

Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; Colonic Neoplasms ; pathology ; Coumarins ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Imines ; chemical synthesis ; chemistry ; pharmacology ; KB Cells ; drug effects ; Liver Neoplasms ; pathology ; Molecular Structure ; Tumor Cells, Cultured ; drug effects

Asthma is characterized by airway inflammation induced by immune dysfunction to inhaled antigens. Although respiratory viral infections are the most common cause of asthma exacerbation, immunologic mechanisms underlying virus-associated asthma exacerbation are controversial. Clinical evidence indicates that nitric oxide (NO) levels in exhaled air are increased in exacerbated asthma patients compared to stable patients. Here, we evaluated the immunologic mechanisms and the role of NO synthases (NOSs) in the development of virus-associated asthma exacerbation. A murine model of virus-associated asthma exacerbation was established using intranasal challenge with ovalbumin (OVA) plus dsRNA for 4 weeks in mice sensitized with OVA plus dsRNA. Lung infiltration of inflammatory cells, especially neutrophils, was increased by repeated challenge with OVA plus dsRNA, as compared to OVA alone. The neutrophilic inflammation enhanced by dsRNA was partly abolished in the absence of IFN-gamma or IL-17 gene expression, whereas unaffected in the absence of IL-13. In terms of the roles of NOSs, dsRNA-enhanced neutrophilic inflammation was significantly decreased in inducible NOS (iNOS)-deficient mice compared to wild type controls; in addition, this phenotype was inhibited by treatment with a non-specific NOS inhibitor (L-NAME) or an specific inhibitor (1400 W), but not with a specific endothelial NOS inhibitor (AP-CAV peptide). Taken together, these findings suggest that iNOS pathway is important in the development of virus-associated exacerbation of neutrophilic inflammation, which is dependent on both Th1 and Th17 cell responses.
Animals ; Asthma/*immunology/virology ; Imines/pharmacology ; Mice ; Mice, Inbred BALB C ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide Synthase Type II/antagonists & inhibitors/*metabolism ; RNA, Double-Stranded/metabolism ; Th1 Cells/*immunology ; Th17 Cells/*immunology

Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.
Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Bicyclo Compounds, Heterocyclic/chemistry/*pharmacology ; Blotting, Western ; Breast Neoplasms/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Survival/drug effects ; Chromatin Immunoprecipitation ; Female ; Gene Expression/drug effects ; Humans ; Imines/chemistry/*pharmacology ; Immunohistochemistry ; Mammary Neoplasms, Experimental/pathology/prevention & control ; Matrix Metalloproteinase 9/genetics/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Structure ; Phosphorylation/drug effects ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor/genetics/*metabolism ; Stilbenes/chemistry ; Xenograft Model Antitumor Assays/methods