Dextrorotatory Chromomycins from the Marine Streptomyces sp. Associated to Palythoa caribaeorum

Abstract

A Streptomyces sp. (BRA-384) was selected among nine strains of bacteria isolated from the zoanthids Palythoa caribaeorum due to the high cytotoxic activity presented by its EtOAc extract (inhibitory concentration mean (IC 50 ) of 2 ng mL -1 ) against colon cancer cell line. From the EtOAc extract of BRA-384 three new chemical entities (A 6 , A 7 and A 8 ) and one dextrorotatory chromomycin (A 5 ), a promising class of anticancer compounds, were identified. The cytotoxicity of chromomycins A 5 to A 8 was tested against five tumor cell lines (HCT 116 (human colon adenocarcinoma), MCF-7 (human breast carcinoma), PC-3M (human metastatic prostate cancer), 501-mel (human metastatic melanoma) and MM200 (metastatic melanoma)). All chromomycins were highly potent showing IC 50 values from 0.2 to 133 nM. Chromomycin A 5 was consistently the most potent over all tested cells (IC 50 values from 0.2 in MM200 to 7.9 nM in PC-3M), inclusive when compared to the standard chemotherapeutic agent doxorubicin, that presented IC 50 values ranging from 147 to 568 nM against MM200 and MCF-7, respectively.