Thongchai Taechowisan

Antitumor activity of 4-arylcoumarins from endophytic Streptomyces aureofaciens CMUAc130.

In a search for antitumor agents, we carried out a screening of 4-arylcoumarins isolated from endophytic Streptomyces aureofaciens CMUAc130, by examining their possible inhibitory effect on the growth of s.c. transplanted Lewis lung carcinoma (LLC) in BDF-1 mice by intraperitoneal (i.p.) administration. The 4-arylcoumarins showed antitumor activity with T/C values of 80.8 and 50.0% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-p-methoxylphenylcoumarin treatment, respectively and 81.5 and 44.9% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-phenylcoumarin treatment, respectively, compared to adriamycin, which was used a positive control, with T/C value of 55.9% at 2 mg/kg. Furthermore, we investigated the possible effects of these compounds on expression of the bcl-2 and Bax oncoproteins in A427, a human lung cancer cell lines. The cells were cultured in vitro for 24 h in RPMI 1640 with 1.5% (v/v) ethanol, 100 microg/ml 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. Viability was determined by an MTT assay. Total protein was extracted from cell lysates and the bcl-2 and Bax oncoproteins were identified. Western blotting showed a decrease in bcl-2 and an increase in Bax in A427 cell cultured with 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. We conclude that 5,7-dimethoxy-4-phenylcoumarin is a more potent inhibitor of cell proliferation than 5,7-dimethoxy-4-p-methoxylphenylcoumarin and has more marked effects on oncoprotein expression.

In vitro anti-inflammatory activity of 4-arylcoumarins from endophytic Streptomyces aureofaciens CMUAc130 in murine macrophage RAW 264.7 cells

This research was undertaken to find the in vitro inflammatory action of 5,7-dimethoxy-4-p-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin produced by Streptomyces aureofaciens CMUAc130. We investigated the effects of 5,7-dimethoxy-4-p-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin not only on the formation of nitric oxide (NO), PGE2, TNF-α, IL-6 and IL-1β, but also on inducible NO synthase and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of iNOS enzyme expression. A similar fashion was also observed when LPS-induced PGE2 release and COX-2 expression were tested. The significant inhibitory effects were shown in concentration-dependent manners. In addition, 5,7-dimethoxy-4-p-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin also mildly but significantly reduced the formation of TNF-α. These findings support the application of 5,7-dimethoxy-4-p-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin as anti-inflammatory agents.

Identification ofStreptomyces sp. Tc022, an endophyte inAlpinia galanga, and the isolation of actinomycin D

Some endophytic actinomycetes (120) were isolated from the roots ofAlpinia galanga. Identification of these endophytes was based on their morphology and amino acid composition of the whole-cell extract. Most isolates were classified aStreptomyces sp. (82), with the remainder belonging toNocardia sp. (11),Microbispora sp. (3) andMicromonospora sp. (2). Eight isolates were unclassified and 14 were lost during subculture. The strain identified as endophyticStreptomyces sp. Tc022 strongly inhibitedColletotrichum musae andCandida albicans. This endophyte was cultured, the agar was extracted with organic solvent and the extract was purified on a column of silica gel to give a major component, which was identified to be actinomycin D on the basis of spectroscopic dat Actinomycin D showed antifungal activity againstColletotrichum musae andCandida albicans with the MIC of 10 and 20 mg ml−1, respectively.

Anti-inflammatory activity of lansais from endophytic Streptomyces sp. SUC1 in LPS-induced RAW 264.7 cells

Abstract This research was undertaken to find the in vitro inflammatory action of lansai A–D produced by Streptomyces sp. SUC1. We investigated the effects of lansai C not only on the formation of nitric oxide (NO), prostaglandin E2 (PGE2), tumour necrosis factor (TNF-α), interleukin (IL)-1α, IL-6 and IL-10, but also on inducible NO synthase and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of inducible nitric oxide synthase enzyme expression. A similar fashion was also observed when LPS-induced PGE2 release and COX-2 expression were tested. The significant inhibitory effects were shown in concentration-dependent manners. In addition, lansai C also mildly but significantly reduced the formation of TNF-α. These findings support the application of lansai C as anti-inflammatory agent.

Synthesis of 1,6,7,8-tetrahydro-naphtho[2,3-d]-azepino[4,5-b]indole-9,14-diones and their inhibitory effects on pro-inflammatory cytokines.

A rapid route to a series of naphthoquinone-fused indole derivatives via irradiation in a modified commercial domestic microwave is reported. The desired products were produced in high yields and short reaction times. The naphthoquinone-fused indole derivatives were evaluated for their pro-inflammatory cytokines responses using lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. The results showed that most of the tested compounds inhibit the production of nitric oxide (NO), prostaglandin (PG)E(2), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-1beta in RAW264.7 cells treated with LPS.

4-arylcoumarin inhibits immediate-type allergy

Abstract This study was undertaken to investigate the effect of 4-arylcoumarin (5,7-dimethoxy-4-p-methoxyphenylcoumarin; MPC) on immediate-type allergic reaction and inflammatory cytokine secretion. MPC inhibited compound 48/80-induced systemic reactions in mice. When MPC was given as a pretreatment at concentrations ranging from 0.001 to 1 g/kg, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. In addition, MPC also inhibited the passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody dose dependently. Furthermore, MPC decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor-α and interleukin-6 secretion in human mast cells. These results indicate that MPC may be beneficial in the treatment of immediate-type allergic reactions.

Anti-inflammatory effects of lansai C and D cause inhibition of STAT-1 and NF-κB activations in LPS-induced RAW 264.7 cells

Abstract In inflammation, proinflammatory cytokines induce the formation of large amounts of nitric oxide (NO) by inducible nitric oxide synthase (iNOS), and compounds that inhibit NO production have anti-inflammatory effects. In the present study, we investigated the effects of lansai C and D on NO production in lipopolysaccharide-induced RAW 264.7 cells, and evaluated the mechanisms of action of the compounds. Lansai C and D inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner. These compounds inhibited the activation of nuclear factor-κB, which is a significant transcription factor for iNOS and also inhibited the activation of the signal transducer and activator of transcription-1, another important transcription factor for iNOS. The present study characterises the effects and mechanisms of lansais on iNOS expression and NO production in activated macrophages. The results explain the pharmacological efficacy of lansais as anti-inflammatory compounds.

Anti-inflammatory effects of 4-arylcoumarins in LPS-induced murine macrophage RAW 264.7 cells

Abstract This research was undertaken to find the in vitro. inflammatory action of 5,7-dimethyloxy-4-p.-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin produced by Streptomyces aureofaciens. CMUAc130. We investigated the effects of 5,7-dimethyloxy-4-p.-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin not only on the formation of NO, prostaglandin E2 (PGE2), and tumor necrosis factor-α. (TNF-α.) but also on inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of iNOS enzyme expression. A similar fashion was also observed when LPS-induced PGE2 release and COX-2 expression were tested. The significant inhibitory effects were shown in concentration-dependent manners. In addition, 5,7-dimethyloxy-4-p.-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin also mildly but significantly reduced the formation of TNF-α.. These findings support the application of 5,7-dimethyloxy-4-p.-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin as anti-inflammatory agents.

Synthesis and anticancer activity of 5,6,8,13-tetrahydro-7H-naphtho[2,3-a][3]-benzazepine-8,13-diones

A series of naphthoquinones fused benzazepines, 5,6,8,13-tetrahydro-7H-naphtho[2,3-a][3]-benzazepine-8,13-diones, were synthesized and evaluated for their anticancer activity against four cell lines; human breast carcinoma cell line, human cervix carcinoma cell line, human hepatocellular carcinoma cell line and human keratinocyte cell line. The results showed that 5,6,8,13-tetrahydro-2,3,4,9-tetramethoxy-7H-naphtho[2,3-a][3]benzazepine-8,13-dione 4g and 5,6,8,13-tetrahydro-2,3,9-trimethoxy-7H-naphtho[2,3-a][3]benzazepine-8,13-dione 4h have significant cytotoxicity against a hepatocellular carcinoma cell line with IC50 = 3.5 μg/mL and 3.0 μg/mL, respectively.

Antibacterial and Anticandidal Activities of New Flavonoids from Streptomyces sp. HK17; an Endophyte in Curcuma longa Linn

Aims: The purpose of this study was to investigate the antibacterial and anticandidal activities of new flavonoids from Streptomyces sp. HK17 which was isolated from the root tissue of Curcuma longa Linn.