Actinopolysporins A–C and Tubercidin as a Pdcd4 Stabilizer from the Halophilic Actinomycete Actinopolyspora erythraea YIM 90600 (original) (raw)
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The present study was conducted to evaluate the antimicrobial and antitumor activities of bioactive compounds produced from locally isolated actinomycetes (KH14), and analyzing these compounds by TLC, bioautograhgy and HPLC-MS. The isolate KH14 showed significant inhibition of human microbial pathogens, both Gram positive, Gram negative bacteria and yeast with an inhibition zone of 30, 13 and 12 mm, respectively. The MICs potential against Staphylococcus aureus, Escherichia coli and Candida albicans were 64, 500 and 500 µl/ml, respectively. The antimicrobial compound was analyzed by TLC, which indicated the presence of four spots while only one of them exhibited antimicrobial activities and their position was determined by bioautography, via different solvents exhibiting different R f values. HPLS-MS analysis of scraped active spot from the TLC indicated the presence of a large number of compounds when determining their mass chromatogram, while UV absorbance indicated the presences of only two peaks with UV absorbances 221.85and 264.85nm. The antitumor activity by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay indicated that KH14possesses a powerful effect against using cancerous cell lines, especially against Breast cancer cells (MCF-7) by inhibiting 75.84% with (400 µg), while against the rest of other cell lines, Human Prostate cancer cells (PC3)and Human malignant melanoma, skin cancer (A375), were shown moderate activities.
Natural Product Reports, 2009
Antitumor compounds produced by actinomycetes and novel derivatives generated by combinatorial biosynthesis are reviewed (with 318 references cited). The different structural groups for which the relevant gene clusters have been isolated and characterized are reviewed, with a description of the strategies used for the generation of the novel derivatives and the activities of these compounds against tumor cell lines.
Antitumor Compounds from Marine Actinomycetes
Marine Drugs, 2009
Chemotherapy is one of the main treatments used to combat cancer. A great number of antitumor compounds are natural products or their derivatives, mainly produced by microorganisms. In particular, actinomycetes are the producers of a large number of natural products with different biological activities, including antitumor properties. These antitumor compounds belong to several structural classes such as anthracyclines, enediynes, indolocarbazoles, isoprenoides, macrolides, non-ribosomal peptides and others, and they exert antitumor activity by inducing apoptosis through DNA cleavage mediated by topoisomerase I or II inhibition, mitochondria permeabilization, inhibition of key enzymes involved in signal transduction like proteases, or cellular metabolism and in some cases by inhibiting tumor-induced angiogenesis. Marine organisms have attracted special attention in the last years for their ability to produce interesting pharmacological lead compounds.
Molecular insights on the biosynthesis of antitumour compounds by actinomycetes
Microbial Biotechnology, 2011
Natural products are traditionally the main source of drug leads. In particular, many antitumour compounds are either natural products or derived from them. However, the search for novel antitumour drugs active against untreatable tumours, with fewer side-effects or with enhanced therapeutic efficiency, is a priority goal in cancer chemotherapy. Microorganisms, particularly actinomycetes, are prolific producers of bioactive compounds, including antitumour drugs, produced as secondary metabolites. Structural genes involved in the biosynthesis of such compounds are normally clustered together with resistance and regulatory genes, which facilitates the isolation of the gene cluster. The characterization of these clusters has represented, during the last 25 years, a great source of genes for the generation of novel derivatives by using combinatorial biosynthesis approaches: gene inactivation, gene expression, heterologous expression of the clusters or mutasynthesis. In addition, these techniques have been also applied to improve the production yields of natural and novel antitumour compounds. In this review we focus on some representative antitumour compounds produced by actinomycetes covering the genetic approaches used to isolate and validate their biosynthesis gene clusters, which finally led to generating novel derivatives and to improving the production yields.
Current approaches to exploit actinomycetes as a source of novel natural products
Journal of Industrial Microbiology & Biotechnology, 2011
For decades, microbial natural products have been one of the major sources of novel drugs for pharmaceutical companies, and today all evidence suggests that novel molecules with potential therapeutic applications are still waiting to be discovered from these natural sources, especially from actinomycetes. Any appropriate exploitation of the chemical diversity of these microbial sources relies on proper understanding of their biological diversity and other related key factors that maximize the possibility of successful identification of novel molecules. Without doubt, the discovery of platensimycin has shown that microbial natural products can continue to deliver novel scaffolds if appropriate tools are put in place to reveal them in a cost-effective manner. Whereas today innovative technologies involving exploitation of uncultivated environmental diversity, together with chemical biology and in silico approaches, are seeing rapid development in natural products research, maximization of the chances of exploiting chemical diversity from microbial collections is still essential for novel drug discovery. This work provides an overview of the integrated approaches developed at the former Basic Research Center of Merck Sharp and Dohme in Spain to exploit the diversity and biosynthetic potential of actinomycetes, and includes some examples of those that were successfully applied to the discovery of novel antibiotics.
Molecular identification of actinomycetes with antimicrobial, antioxidant and anticancer properties
Comunicata Scientiae
The objectives of this study were to isolate and identify the actinomycetes strains from the soil and marine sediments and to evaluate the antimicrobial, antioxidant and cytotoxic activity of their bioactive secondary metabolites. Eight actinomycetes strains were isolated from soil and marine sediment samples collected from different areas in Egypt. Only three actinomycetes exhibited a wide spectrum of antimicrobial activities. They were active in vitro against microbial pathogen viz: Staphylococcus aureus, Escherichia coli, Salmonella typhi, Aspergillus parasiticus, Fusarium solani and Fusarium oxysporum. These promising isolates were selected and identified using molecular identification technique and identified as Streptomyces spp. The crude extracts from the three Streptomyces exhibited potent antimicrobial activities against a set of microbial pathogens as well as antioxidant and anticancer activity in human hepatocellular carcinoma cell line (HepG2). The crude extract of Strep...
Journal of Natural Products, 2022
Chemical investigation of the fermentation products of a deep sea water-derived actinomycete, Actinomadura sp. KD439, identified seven new angucyclinones, designated as kumemicinones A−G (1−7), together with the known SF2315B and miaosporone E. NMR and MS spectroscopic analyses, combined with X-ray crystallography and quantum chemical calculations of NMR chemical shifts and electronic circular dichroism (ECD) spectra, uncovered the structures of new angucyclinones as regioisomers of SF2315B at the allyl alcohol unit (1 and 2), an epoxy ring-opened γ-hydroxy enone isomer (3), a B/C-ring-rearranged product (4), or dimers with a new mode of bridging (5−7), adding new structural variation to this antibiotic group. The absolute configuration of SF2315B was also determined by comparison of ECD spectra with those of 1 and 2. All the angucyclinones exhibited cytotoxicity against P388 murine leukemia cells, with IC 50 values ranging from 1.8 to 53 μM.
Journal of natural products, 2016
Three new 10-membered macrolides, saccharothriolides D-F (1-3), were isolated from a rare actinomycete, Saccharothrix sp. A1506. The planar structures were determined from analysis of extensive NMR and HR-ESI-MS data, and the absolute configurations were established by ECD spectroscopy analysis. Saccharothriolides D (1) and E (2) were determined to be C-2 epimers of saccharothriolides A (4) and B (5), respectively. Saccharothriolide F (3) was identified to be a demethylated congener of saccharothriolides D (1) and A (4) at the C-2 position. The availability of compounds 1-6 enabled a structure-activity relationship study that revealed the importance of the phenolic hydroxy group at C-2″ and the stereochemistry of C-2 for the inhibition of human fibrosarcoma HT1080 cell growth.
Natural product communications, 2010
One hundred and twenty-six mesophilic Actinomycete cultures were isolated from the Aegean region of Turkey. The antimicrobial activities of pure isolates were tested using the agar-plaque method. Based on high antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli O157-H7 (E. coli), the isolate M-33-5 was selected for bioactivity-guided isolation. Fermentation, followed by solvent partition (H2O-EtOAc, H2O-n-BuOH), showed that the highest activity was present in the EtOAc extract. By using chromatographic methods, two bioactive compounds were isolated and their structures were determined by spectral methods to be 4'-deacetyl griseusin A and griseusin A. The MIC values of griseusin A and 4'-deacetyl griseusin A against MRSA and E. coli were < or = 1.0 microg/mL. The cytotoxicities of the EtOAc extract and 4'-deacetyl griseusin A were also evaluated against two cancer cell lines (human servical cancer: HeLa; murine fibrobl...