New phenoxazinone-related alkaloids from strain Streptomyces sp. KIB-H1318

Abstract

Chemical investigation of a strain Streptomyces sp. KIB-H1318 isolated from soil sample led to the discovery of three new phenoxazinone-related alkaloids 13, as well as two known analogs exfoliazone (4) and viridobrunnine A (5). Their structures were determined on the basis of extensive spectroscopic analysis. The antimicrobial activity and cytotoxicity of the isolates were assayed. Exfoliazone and viridobrunnine A exhibited minor antibacterial activity against Escherichia coli ATCC 8099, Bacillus subtilis ATCC 6633, and Staphylococcus aureus ATCC 6538. Compound 2 exhibited low cytotoxicity against two human cancer cell lines HeLa and SW480 with the IC50 values of 36.8 and 37.8 μM, respectively.

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References

  1. 1.

    Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. 2016;79:629–61.

  2. 2.

    Yan Y, et al. Tropolone ring construction in the biosynthesis of rubrolone B, a cationic tropolone alkaloid from endophytic Streptomyces. Org Lett. 2016;18:1254–7.

  3. 3.

    Yang R, et al. α-Pyrone derivatives from a Streptomyces strain resensitize tamoxifen resistance in breast cancer cells. Nat Prod Bioprospect. 2017;7:329–34.

  4. 4.

    Shang N, et al. Glycosylated piericidins from an endophytic Streptomyces with cytotoxicity and antimicrobial activity. J Antibiot. 2018;71:672–6.

  5. 5.

    Imai S, et al. Isolation and structure of a new phenoxazine antibiotic, exfoliazone, produced by Streptomyces exfoliatus. J Antibiot. 1990;43:1606–7.

  6. 6.

    Ren J, et al. Venezuelines A-G, new phenoxazine-based alkaloids and aminophenols from Streptomyces venezuelae and the regulation of gene target Nur77. Bioorg Med Chem Lett. 2013;23:301–4.

  7. 7.

    Gomes PB, Nett M, Dahse HM, Hertweck C. Pitucamycin: structural merger of a phenoxazinone with an epoxyquinone antibiotic. J Nat Prod. 2010;73:1461–4.

  8. 8.

    Merkel O, et al. Actinomycin D induces p53-independent cell death and prolongs survival in high-risk chronic lymphocytic leukemia. Leukemia. 2012;26:2508–16.

  9. 9.

    Shimizu S, et al. Phenoxazine compounds produced by the reactions with bovine hemoglobin show antimicrobial activity against non-tuberculosis mycobacteria. Tohoku J Exp Med. 2004;203:47–52.

  10. 10.

    Hayashi K, Hayashi T, Miyazawa K, Tomoda A. Phenoxazine derivatives suppress the infections caused by herpes simplex virus type-1 and herpes simplex virus type-2 intravaginally inoculated into mice. J Pharmacol Sci. 2010;114:85–91.

  11. 11.

    Blank B, Baxter LL. Synthesis and antiinflammatory screening of phenoxazine-1-carboxylic acids. J Med Chem. 1968;11:807–11.

  12. 12.

    Monks A, et al. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst. 1991;83:757–66.

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Acknowledgements

This research was financially supported by the National Natural Science Foundation of China to S-X.H. (Nos. U1702285 and 81522044), Yunnan Innovative Research Team for Discovery and Biosynthesis of Bioactive Natural Products (2018HC012), High-end Science and Technology Talents Program of Yunnan Province to S-X.H. (No. 2013HA022), and Key Research Program of Frontier Sciences, CAS (No. QYZDB-SSW-SMC051).

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Correspondence to Sheng-Xiong Huang.

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