A new cytotoxic phenazine derivative from a deep sea bacterium Bacillus sp

Key Laboratory of Marine Drugs, Chinese Ministry of Education, Institute of Marine Drugs and Food, Ocean University of China, Qingdao 266003, PR China.
Archives of Pharmacal Research (Impact Factor: 2.05). 06/2007; 30(5):552-5. DOI: 10.1007/BF02977647
Source: PubMed

ABSTRACT A novel phenazine derivative (1) together with six known compounds (2-7) were isolated by bioassay-guided fractionation from the culture broth of a bacterium, Bacillus sp., collected from a Pacific deep sea sediment sample (depth 5059 m). The structures of these compounds were determined using spectroscopic methods. Their cytotoxic effects on P388 and K562 cell lines were preliminarily examined using the sulforhodamine-B (SRB) assay.

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Available from: Dehai Li, May 15, 2014
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    • "The phenazine antibiotics isolated from Bacillus sp. of Pacific deep-sea sediment (depth of 5059 m) possessed anticancer activity on P388 cancer cell line. The antibiotics such as 5,10- dihydrophencomycin methyl ester and phencomycin (isolated from an unidentified marine Streptomyces sp.) [23] have weak activity against E. coli and B. subtilis [24]. N-(2-hydroxyphenyl)-2-phenazinamine isolated from marine actinomycete (BM-17) has cytotoxicity against K562, HepG2, MGC803, HCT116 and MCF7 cancer cell lines, as well as 293T non-cancer cell line [25]. "
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    ABSTRACT: Fused aryl phenazine derivatives especially benzo[a]phenazine, pyrido[a]phenazine, benzo[a]phenazine diones, tetrahydropyrido[a]phenazine (dermacozines), etc are important heterocyclic compounds exhibit various pharmacological activities, prominently in cancer cell lines. These compounds significantly intercalating with DNA and inhibit the activity of topoisomerase I and II enzymes (Topo I and II). XR11576, XR5944, NC-190 and NC-182 are belonging to this category, which are under clinical studies. Many fused aryl phenazine dione derivatives such as pyridazino[4,5-b]phenazine-5,12-diones, 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-diones, 6,11-dihydro-benzo[2,3-b]phenazine-6,11-diones, tetrahydropyrido[a]phenazine, etc have anticancer activity against various cancer cell lines. Benzo[a]phenazine diimine and other fused aryl phenazine compounds form coordination complex with the metal ions such as Ru, Rh, Zn and Pt that intercalate with the DNA and are used for the treatment of cancer. These molecules also possessed anticancer activity on MDR cancer cells and act as MDR modulating agents. The structure activity relationship of the fused aryl phenazine derivatives revealed that the presence of four or more nitrogen atoms in the compounds possessed better anticancer activity than molecules with less number of nitrogen atoms. Phenazine antibiotics derived from marine microbes are used for the treatment of microbial and worm diseases. Recent patent on these scaffolds showed that the benzo[a]phenazine derivatives possessed inhibitory activity on topoisomerase enzymes (Topo I and II), which act as anticancer agents and also used for the treatment of autoimmune disease and inflammatory conditions.
    Current drug targets 02/2014; 15(7). DOI:10.2174/1389450115666140205152007 · 3.02 Impact Factor
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    • "Lately, Homann et al. reported the isolation of peptidic siderophores Loihichelins A-F [8] from the cultures of heterotrophic bacterium Halomonas LOB-5 collected from the southern rift zone of Loihi Seamount east of Hawaii. Novel cytotoxic phenazine derivatives [9] with unique ring system have been described from pacific sediment Bacillus sp. (5059 m depth). "
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    ABSTRACT: Background High salinity and temperature combined with presence of heavy metals and low oxygen renders deep-sea anoxic brines of the Red Sea as one of the most extreme environments on Earth. The ability to adapt and survive in these extreme environments makes inhabiting bacteria interesting candidates for the search of novel bioactive molecules. Methods Total 20 i.e. lipophilic (chloroform) and hydrophilic (70% ethanol) extracts of marine bacteria isolated from brine-seawater interface of the Red Sea were tested for cytotoxic and apoptotic activity against three human cancer cell lines, i.e. HeLa (cervical carcinoma), MCF-7 (Breast Adenocarcinoma) and DU145 (Prostate carcinoma). Results Among these, twelve extracts were found to be very active after 24 hours of treatment, which were further evaluated for their cytotoxic and apoptotic effects at 48 hr. The extracts from the isolates P1-37B and P3-37A (Halomonas) and P1-17B (Sulfitobacter) have been found to be the most potent against tested cancer cell lines. Conclusion Overall, bacterial isolates from the Red Sea displayed promising results and can be explored further to find novel drug-like molecules. The cell line specific activity of the extracts may be attributed to the presence of different polarity compounds or the cancer type i.e. biological differences in cell lines and different mechanisms of action of programmed cell death prevalent in different cancer cell lines.
    BMC Complementary and Alternative Medicine 02/2013; 13(1):29. DOI:10.1186/1472-6882-13-29 · 2.02 Impact Factor
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    • "Structural investigations identified the two pigments as novel phenazostatin D, inactive against the tested microorganisms, and methyl saphenate, a known phenazine antibiotic. Li et al. [64] also reported the isolation of a novel phenazine derivative with cytotoxic effects against P388 cells, together with six previously identified compounds from the marine Bacillus sp., collected from a Pacific deep-sea sediment sample at a depth of 5059 m. A novel phenazine derivative with antibiotic activity, identified as 5,10-dihydrophencomycin methyl ester, along with (2-hydroxyphenyl)-acetamide, menaquinone MK9 (II, III, VIII, IX-H8), and phencomycin, was isolated from an unidentified marine Streptomyces sp. by Pusecker et al. [65]. "
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    ABSTRACT: Research into natural products from the marine environment, including microorganisms, has rapidly increased over the past two decades. Despite the enormous difficulty in isolating and harvesting marine bacteria, microbial metabolites are increasingly attractive to science because of their broad-ranging pharmacological activities, especially those with unique color pigments. This current review paper gives an overview of the pigmented natural compounds isolated from bacteria of marine origin, based on accumulated data in the literature. We review the biological activities of marine compounds, including recent advances in the study of pharmacological effects and other commercial applications, in addition to the biosynthesis and physiological roles of associated pigments. Chemical structures of the bioactive compounds discussed are also presented.
    Evidence-based Complementary and Alternative Medicine 09/2011; 2011(3):670349. DOI:10.1155/2011/670349 · 1.88 Impact Factor
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