Synthesis of isomeric, oxathiolone fused chalcones, and comparison of their activity toward various microorganisms and human cancer cells line. (73/302)

Isomeric oxathiolone fused chalcones were prepared by condensation of appropriate acetylbenzo[1,3]oxathiol-2-ones with benzaldehydes under acidic conditions. The synthesized compounds were screened for cytotoxic activity using HeLa cells, as well as for antibacterial activity against Micrococcus luteus, Staphylococcus aureus, Salmonella typhimurium, Escherichia coli, Proteus vulgaris, antifungal activity against Candida albicans, and tuberculostatic activity against Mycobacterium tuberculosis H(37)Rv and Mycobacterium kansasii strains.  (+info)

An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis. (74/302)

BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.  (+info)

One-pot synthesis of highly conjugated benzofuran derivatives based on electrochemical oxidation of benzenediols in the presence of dibenzoylmethane. (75/302)

Electrochemical oxidation of benzenediols (1--4) has been studied in the presence of dibenzoylmethane (5) as a nucleophile using cyclic voltammetry and controlled-potential coulometry. The results indicate that the electrochemically generated quinones participate in Michael addition reaction with 5 via various mechanisms to produce new benzofuran derivatives. We derived various products based on electrochemical oxidation in the controlled potential condition, at carbon electrode without toxic reagents in an undivided cell and ambient condition.  (+info)

Selected flavonoids potentiate the toxicity of cisplatin in human lung adenocarcinoma cells: a role for glutathione depletion. (76/302)

Adjuvant therapies that enhance the anti-tumor effects of cis-diammineplatinum(II) dichloride (cisplatin, CDDP) are actively being pursued. Growing evidence supports the involvement of mitochondrial dysfunction in the anti-cancer effect of cisplatin. We examined the potential of using selective flavonoids that are effective in depleting tumor cells of glutathione (GSH) to potentiate cisplatin-mediated cytotoxicity in human lung adenocarcinoma (A549) cells. We found that cisplatin (40 microM, 48-h treatment) disrupts the steady-state levels of mitochondrial respiratory complex I, which correlates with elevated mitochondrial reactive oxygen species (ROS) production and cytochrome c release. The flavonoids, 2',5'-dihydroxychalcone (2',5'-DHC, 20 microM) and chrysin (20 microM) potentiated the cytotoxicity of cisplatin (20 microM), which could be blocked by supplementation of the media with exogenous GSH (500 microM). Both 2',5'-DHC and chrysin were more effective than the specific inhibitor of GSH synthesis, L-buthionine sulfoximine (BSO, 20 microM), in inducing GSH depletion and potentiating the cytotoxic effect of cisplatin. These data suggest that the flavonoid-induced potentiation of cisplatin's toxicity is due, in part, to synergetic pro-oxidant effects of cisplatin by inducing mitochondrial dysfunction, and the flavonoids by depleting cellular GSH, an important antioxidant defense.  (+info)

Suppression of androgen receptor expression by dibenzoylmethane as a therapeutic objective in advanced prostate cancer. (77/302)

BACKGROUND: The androgen receptor (AR) plays an important role in the development and progression of prostate cancer. Functional AR expression persists in most cases of hormone-refractory prostate cancer and may play a role clinically in the progression from hormone-responsive to hormone-refractory or advanced prostate cancer. In order to combat the progression of this disease, one needs to identify new chemotherapeutic agents with novel mechanisms of action. MATERIALS AND METHODS: In this study, we attempt to clarify the molecular mechanism by which dibenzoylmethane (DBM), a beta3-diketone, inhibits the growth of androgen-responsive human LNCaP prostate cancer cells and down-regulates expression of the AR. To this end, we treated LNCaP cells with different concentrations of DBM to monitor function and expression of AR and an AR-associated protein. RESULTS: Previous studies showed that DBM could inhibit cell proliferation in LNCaP cells by arresting the cells at the G1 phase without causing cell death. Western blot and RT-PCR/Northern blot analyses showed a reduction in AR protein and mRNA expression by DBM in a dose-dependent manner. Furthermore, stable transfections of an androgen-independent human prostate cancer cell line, transfected with a full-length human AR cDNA sequence, showed that DBM down-regulated AR protein levels. DBM also inhibited the secretion of the AR-regulated tumor marker, prostate-specific antigen (PSA). Moreover, the relative binding affinity of DBM to AR was lower than that of the synthetic androgen R1881 (methyltrienolone) suggesting that DBM must suppress AR expression independent of an AR-DBM bound interaction. CONCLUSION: These data provide new insights into how DBM regulates AR function and cell growth, as well as providing promising evidence to support DBM as a chemotherapeutic agent for prostate cancer through suppression of the function of the androgen receptor.  (+info)

Constituent properties of licorices derived from Glycyrrhiza uralensis, G. glabra, or G. inflata identified by genetic information. (78/302)

Constituent properties of licorices derived from Glycyrrhiza uralensis, G. glabra, and G. inflata are revealed by comparing 117 of licorice identified using four genetic markers; internal tracscribed spacer (ITS) on nuclear ribosomal DNA, rbcL gene, matK gene, and trnH-trnK1 intergenic region on chloroplast DNA. Regarding six main constituents of licorice; glycyrrhizin, liquiritin, liquiritin apioside, isoliquiritin, isoliquiritin apioside, and liquiritigenin, the constituent property of G. glabra resembles to that of G. inflata. On the other hand, the constituent property of G. uralensis is not similar to that of G. glabra or G. inflata and is characterized by a wide content variation of the six constituents compared to those of G. glabra and/or G. inflata. The mean contents of liquiritin, isoliquiritin, or liquilitigenin in G. uralensis are significantly higher than those of G. glabra or G. inflata. Therefore, the licorice species should be selected depending on these constituent properties for the traditional Chinese medicines or the Japanese Kampo medicines. Additionally, glycycoumarin, glabridin, and licochalcone A were reconfirmed as the species-specific typical constituents of G. uralensis, G. glabra, and G. inflata respectively. Therefore, it is resulted that the determination of the three species-specific constituents may be useful for the species identification of licorice. However, since 6% of licorice examined and hybrids were exceptions to the rule, their genetic information is necessary for the accurate species identification of licorice.  (+info)

Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-alpha, CH11 and CYC202. (79/302)

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear hormone superfamily and has multiple endogenous and pharmacological ligands, including 15-deoxy-Delta (12,14)-prostaglandin J(2) and two thiazolidinediones (TZD), rosiglitazone and pioglitazone, which are used clinically to treat type-2 diabetes mellitus. PPARgamma agonists regulate development, cellular growth and metabolism in various tissues and have been documented to decrease cellular proliferation and to induce apoptosis of various tumour phenotypes, including breast cancer. However, the full spectrum of anti-tumour effects occurs only at suprapharmacological doses. In this study, we investigated the mechanism of rosiglitazone-induced anti-tumour effects of MDA-MB-231 human breast cancer cells, and used that information to predict rosiglitazone-induced sensitization of breast cancer cells to the effects of other compounds. We first confirmed that 100 microM rosiglitazone, but not lower doses, decreases MDA-MB-231 cell viability in vitro. We then used microarray gene expression analysis to determine early rosiglitazone-induced gene expression changes after 4-h exposure, which included 1298 genes that we grouped into functional categories. We selectively confirmed rosiglitazone-mediated effects on expression of key regulators of breast cancer proliferation and apoptosis, including p53, p21 and Bax. Finally, we used this information to predict that rosiglitazone would sensitize MDA-MB-231 cells to the anti-tumour effects of CH11, which trimerizes Fas, as well as tumour necrosis factor-alpha. Moreover, we used the confirmed array data to predict cooperative activity of rosiglitazone and R-roscovitine (CYC202), an inhibitor of multiple cyclin-dependent kinases. We conclude that microarray analysis can determine early TZD-modulated changes in gene expression that help to predict effective in vitro drug combinations.  (+info)

Anti-inflammatory activity of the synthetic chalcone derivatives: inhibition of inducible nitric oxide synthase-catalyzed nitric oxide production from lipopolysaccharide-treated RAW 264.7 cells. (80/302)

Chalcones belong to the flavonoid family from plant origin and some of them possess anti-inflammatory activity. Recently, several natural and synthetic chalcone derivatives were reported to inhibit inducible nitric oxide synthase (iNOS)-catalyzed NO production in cell cultures. In the present study, to find the optimal chemical structures and to elucidate their action mechanisms, 41 synthetic chalcones having the substituent(s) on A- and B-rings were prepared and their effects on iNOS-catalyzed NO production were evaluated using lipopolysaccharide (LPS)-treated RAW 264.7 cells. When simultaneously added with LPS, 2'-methoxy-3,4-dichlorochalcone (Ch15), 2'-hydroxy-6'-methoxychalcone (Ch29), 2'-hydroxy-3-bromo-6'-methoxychalcone (Ch31) and 2'-hydroxy-4',6'-dimethoxychalcone (Ch35) among the tested compounds potently inhibited NO production (IC(50)s, 7.1-9.6 muM). The favorable chemical structures were found to be a methoxyl substitution in A-ring at an adjacent position (2' or 6') to carbonyl moiety with/without 2'-(or 6'-)hydroxyl group and 3-halogen substitution in B-ring. When the cellular action mechanisms of Ch15, Ch31 and Ch35 were further examined using Western blotting and electrophoretic mobility shift assay, it was revealed that Ch15 and Ch31 clearly down-regulated iNOS expression while Ch35 did not. Moreover, Ch15 and Ch31 were proved to suppress the nuclear transcription factor-kappaB activation. From the results, it is suggested that certain chalcone derivatives potently inhibit iNOS-catalyzed NO production by the different cellular mechanisms, iNOS down-regulation and/or iNOS inhibition, depending on their chemical structures. These chalcone derivatives may possibly be used as lead compounds for developing new anti-inflammatory agents.  (+info)