Cytotoxicity activity of geldanamycin derivatives against various cancer cell lines

Geldanamycin (1) was isolated as a major compound from Streptomyces zerumbet W14. It was then used as a precursor tosynthesize two new geldanamycins: 17-(tryptamine)-17-demethoxygeldanamycin (2) and 17-(5′-methoxytryptamine)-17-demethoxygeldanamycin (3). The cytotoxicity activity of these two new compounds was evaluated and comparedwith the cytotoxicity of compound 1. Cytotoxicity activity was evaluated against a normal cell line, and three cancercell lines using an 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. Thesolubility of these compounds was also determined. The solubility of compounds 2 and 3 in water was 290.69and 348.18 µM, higher than that of compound 1 by about 1.91 and 2.29 times, respectively. Compounds 2 and 3showed moderate cytotoxic activity on Vero and human cervical carcinoma cells with IC50 values of >200.00 µg/ml. The strongest cytotoxicity of compound 3 was observed in human breast carcinoma cells (MCF-7) and humanhepatocellular carcinoma cell line (HepG2) cells with IC50 values of 82.50 and 114.35 µg/ml, respectively, while theIC50 values of compound 2 against MCF-7 and HepG2 cells were 105.62 and 124.57 µg/ml, respectively. The findingsshowed that these new geldanamycin derivatives exhibited selective cytotoxicity toward some cancer cells at a lowerconcentration. Therefore, future studies on these compounds could be useful for the management of some cancers

Antiviral activity of geldanamycin and its derivatives against influenza virus

Two new geldanamycin derivatives such as 17-(tryptamine)-17-demethoxygeldanamycin (2) andC17 methoxyl of geldanamycin (1). Their antiviral activity was evaluated based on influenza virus propagation inembryonated chicken eggs and viral absorption by hemagglutination (HA) inhibition test. The findings indicatedthat these compounds inhibited viral propagation at a concentration of 12.5 µg/ml. For the viral absorption, onlycompounds 2 and 3 inhibited HA at a concentration of 50 µg/ml. The solubility of compounds 2 and 3 in waterwas 290 and 306 µM, higher than that of compound 1 about 1.91 and 2.01 times, respectively. The compounds 2and 3 showed a moderate cytotoxic activity on LLC-MK2 and Vero cells with IC50 values of >200.00 µg/ml. Theseresults demonstrated the invention of tryptamine-geldanamycin hybrids to prevent influenza virus infection in viralabsorption and viral propagation steps.

Antibacterial and Antioxidant Activities of Acetogenins from Streptomyces sp. VE2; An Endophyte in Vernonia cinerea (L.) Less.

Strain VE2 was isolated from the stem tissue of Vernonia cinerea (L.) Less. and identified as Streptomyces sp. on the basis of morphology, chemotaxonomy and 16SrDNA sequencing. The fractionation of the crude ethyl acetate (CEA) extract from VE2 cultures led to the isolation of two acetogenins; squamocin and rollidecin B; these compounds and CEA extract had potential in antibacterial and antioxidant activities. The crude extract showed the highest activity against Salmonella typhi ATCC19430 and Bacillus cereus ATCC7064, with MIC values of 32 µg/ml. Squamocin also showed the lowest MIC (32 µg/ml) and Minimum Bactericidal Concentration (MBC) (128 µg/ml) against S. Typhi and B. cereus with corresponding large diameter of the zone of inhibitions (27.5 and 28.2 mm, respectively). Rollidecin B showed the highest DPPH antioxidant activity with SC50 value of 58.92 µg/ml.

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. Study Design: Experimental study. Place and Duration of Study: The study was carried out at the Department of Microbiology and Department of Chemistry, Faculty of Science, Silpakorn University, between February and May 2014. Methodology: The major active ingredients from the crude extract were purified by silica gel column chromatography, thin-layer chromatography. The diameters of the zones of inhibition and the Minimum Inhibitory Concentration (MIC) were determined using the paper disc diffusion and the microbroth dilution methods respectively. Results: The crude extract and purified compounds were tested for their antibacterial activity against Staphylococcus aureus ATCC25932, Bacillus cereus ATCC7064 and Bacillus subtilis ATCC6633, Escherichia coli ATCC10536 and Pseudomonas aeruginosa ATCC27853 and anticandidal activity against Candida albicans ATCC190088. The crude extract showed the highest activity against S. aureus and C. albicans, with MIC values of 32 μg/ml. The purified compounds 3 showed the lowest MIC (32 μg/ml) and Minimum Microbicidal Concentration (MMC) (128 μg/ml) against S. aureus and C. albicans with corresponding large diameter of the zone of inhibitions (25.5 and 25.2 mm respectively). Conclusion: This study has shown that the new flavonoids were first isolated and identified. These flavonoids produced by Streptomyces sp. HK17 have potential in antibacterial and anticandidal activities.

Antibacterial activity of new flavonoids from Streptomyces sp. BT01; an endophyte in Boesenbergia rotunda (L.) Mansf.

Strain BT01 was isolated from the root tissue of Boesenbergia rotunda (L.) Mansf. and identified as Streptomyces sp. on the basis of morphology, chemotaxonomy and 16SrDNA sequencing. It was an antagonist of Gram positive bacteria; Staphylococcus aureus ATCC25932, Bacillus cereus ATCC7064 and Bacillus subtilis ATCC6633. The inhibitory effect of the crude extract from the strain BT01 was examined based on the paper disc diffusion method (5 mg per paper disc) with three replications. It has been shown to have antibacterial activity. The major active ingredients from the crude extract were purified by silica gel column chromatography, thin-layer chromatography and identified to be two new flavonoids, 7-methoxy-3, 3',4',6-tetrahydroxyflavone (1) and 2',7-dihydroxy-4',5'-dimethoxyisoflavone (4), together with four known compounds, fisetin (2), naringenin (3), 3'-hydroxydaidzein (5) and xenognosin B (6). Bioassay studies showed that these compounds had antibacterial activity with the minimum inhibitory concentrations within the range of 32 to 256 μg/ml.

Antibacterial activity of Decursin from Streptomyces sp. GMT-8; an endophyte in Zingiber officinale Rosc.

Strain GMT-8 was isolated from the root tissue of Zingiber officinale Rosc. and identified as Streptomyces sp. on the basis of morphology, chemotaxonomy and 16SrDNA sequencing. It was an antagonist of Gram positive bacteria; Staphylococcus aureus ATCC25932, Bacillus cereus ATCC7064 and Bacillus subtilis ATCC6633. The inhibitory effect of the crude extract from the strain GMT-8 was examined based on the paper disc diffusion method (5 mg per paper disc) with three replications. It has been shown to have inhibitory activity against Gram positive bacteria. The major active ingredient from the crude extract was purified by silica gel column chromatography, thin-layer chromatography and identified to be decursin by NMR and mass spectral data, respectively. Bioassay studies showed that decursin had antibacterial activities against Gram positive bacteria with the minimum inhibitory concentrations within the range of 32 to 256 μg/ml.

Antibacterial activity of 1-methyl ester-nigericin from Streptomyces hygroscopicus BRM10; an endophyte in Alpinia galanga.

Strain BRM10 was isolated from the root tissues of Alpinia galanga Swartz. and identified as Streptomyces hygroscopicus BRM10 on the basis of morphology, chemotaxonomy and 16SrDNA sequencing. It was an antagonist of some bacteria, Staphylococcus aureus ATCC25932, Bacillus cereus ATCC6633, Escherichia coli ATCC10536 and Pseudomonas aeruginosa ATCC27853. The culture filtrate and the crude extract from S. hygroscopicus BRM10 were all inhibitory to tested bacteria. The major active ingredients from the crude extract were purified by silica gel column chromatography, thin-layer chromatography and identified to be 1-methyl ester-nigericin (compound 1) and nigericin (compound 2) by NMR and mass spectral data, respectively. Bioassay studies showed that compound 1 had antibacterial activity against Gram positive bacteria lower than compound 2, and its minimum inhibitory concentrations against Staphylococcus aureus ATCC25932 and Bacillus cereus ATCC6633 were 0.5 μg/ml and 1.0 μg/ml, respectively and no inhibitory activity was observed against Escherichia coli ATCC10536 and Pseudomonas aeruginosa ATCC27853, at a concentration of 64 μg/ml.

Antifungal activity of 3-methylcarbazoles from Streptomyces sp. LJK109; an endophyte in Alpinia galangal.

Strain LJK109 was isolated from the root tissues of Alpinia galanga (L.) Willd. and identified as Streptomyces sp. on the basis of morphology, chemotaxonomy and 16SrDNA sequencing. It was an antagonist of phytopathogenic fungi; Alternaria porri, Colletotrichum gloeosporioides, Colletotrichum musae, Curvularia sp., Drechslera sp., Exserohilum sp., Fusarium oxysporum, Verticillium sp. and Sclerotium rolfsii. The culture filtrate and the crude extract from Streptomyces sp. LJK109 were all inhibitory to tested phytopathogenic fungi. The major active ingredients from the crude extract were purified by silica gel column chromatography, thin-layer chromatography and identified to be 3-methylcarbazole (compound 1) and 1-methoxy-3-methylcarbazole (compound 2) by NMR and mass spectral data, respectively. Bioassay studies showed that compound 1 and 2 had antifungal activities against tested fungi, and its minimum inhibitory concentrations were found to be within the range of 30 to 240 μg/ml. Conidia germination was also inhibited by these compounds as determined by microscopy.

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.