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Heliomycin and tetracinomycin D: anthraquinone derivatives with histone deacetylase inhibitory activity from marine sponge-associated Streptomyces sp. SP9

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Abstract

Several actinomycetes strains were isolated from different marine sponges collected from the Red Sea shore in Egypt. The efficiency of their crude extracts to inhibit histone deacetylase (HDAC) enzyme was investigated in the nuclear extract of Hela cell line. The crude extract corresponding to Streptomyces sp. SP9 isolated from the marine sponge Pseudoceratina arabica showed a promising HDAC inhibitory activity with 64 and 81% at 50 and 100 µg/ml, respectively. The strain was identified as Streptomyces sp. by phylogenetic analyses based on its 16S rRNA gene sequence. The major compounds of Streptomyces sp. SP9 were isolated and purified by different chromatographic methods. The chemical structure of the isolated compounds was identified on the basis of their spectroscopic data including mass, 1H and 13C NMR, and by comparison with those of authenticated samples. Structures of compounds 1 and 2 were established as heliomycin and tetracenomycin D, respectively. These compounds exhibited HDAC inhibitory activities with IC50 values of 29.8 ± 0.04 µg/ml for heliomycin (1) and 10.9 ± 0.02 µg/ml for tetracenomycin D (2). A computational docking study for compounds 1 and 2 against HDAC1, HDAC2, and HDAC3 was performed to formulate a hypothetical mechanism by which the tested compounds inhibit HDAC. Tetracenomycin D (2) showed a good binding interactions with HDAC2 (− 5.230 kcal/mol) and HDAC3 (− 6.361 kcal/mol).

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Acknowledgements

The authors are grateful for the financial support from Science and Technology Development Fund (STDF) in Egypt (Grant no. 6884). We thank Professor Rob van Soest (University of Amsterdam, Netherlands) for taxonomic identification of the sponge.

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Authors and Affiliations

  1. Marine Natural Products Unit (MNPRU), Faculty of Science, Helwan University, Ain Helwan, 11795, Cairo, Egypt

    Mohamed Saleh Abdelfattah, Mohammed Ismail Youssef Elmallah & Ali Mohamed Salah Hebishy

  2. Chemistry Department, Faculty of Science, Helwan University, Ain Helwan, 11795, Cairo, Egypt

    Mohamed Saleh Abdelfattah, Mohammed Ismail Youssef Elmallah, Ali Mohamed Salah Hebishy & Neama Hassan Ali

  3. Botany and Microbiology Department, Faculty of Science, Helwan University, Ain Helwan, 11795, Cairo, Egypt

    Ahmed Hassan Ibrahim Faraag

  4. Faculty of Science, Bioinformatics Center, Helwan University, Ain Helwan, 11795, Cairo, Egypt

    Ahmed Hassan Ibrahim Faraag

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  1. Mohamed Saleh Abdelfattah
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  2. Mohammed Ismail Youssef Elmallah
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  3. Ahmed Hassan Ibrahim Faraag
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  4. Ali Mohamed Salah Hebishy
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  5. Neama Hassan Ali
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Correspondence to Mohamed Saleh Abdelfattah.

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Abdelfattah, M.S., Elmallah, M.I.Y., Faraag, A.H.I. et al. Heliomycin and tetracinomycin D: anthraquinone derivatives with histone deacetylase inhibitory activity from marine sponge-associated Streptomyces sp. SP9. 3 Biotech 8, 282 (2018). https://doi.org/10.1007/s13205-018-1304-1

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