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

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, 1 H and 13 C 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 IC 50 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).