Pyramidamycins A-D and 3-hydroxyquinoline-2-carboxamide; cytotoxic benzamides from Streptomyces sp DGC1

Four new benzamides, pyramidamycins A-D (2-5) along with the new natural 3-hydroxyquinoline-2-carboxamide (6) were isolated from the crude extract of Streptomyces sp. DGC1. Additionally, five other known compounds, namely 2-aminobenzamide (anthranilamide) (1), 4',7-dihydroxyisoflavanone (7), 2'-deoxy-thymidine, 2'-deoxy-uridine and adenosine were also isolated and identified. The structures of the new compounds 2-6 were elucidated by 1D and 2D NMR studies along with HR MS analyses. The isolated compounds 1-6 contained the same amide side chain. The isolated compounds 1-7 were biologically evaluated in comparison with landomycin A against a prostate cancer cell line (PC3) and non-small cell lung cancer cell line (H460) for 48 h and against several bacterial strains. Pyramidamycin C (4) was the most active compound against both PC3 and H460 cell lines (GI(50) = 2.473 and 7.339 mu M, respectively). Benzamides (1-3) demonstrated inhibitory activity against Kocuria rosea B-1106 (a diameter halo of 13 +/- 2 mm for 1; 10 +/- 2 mm for 2 and 3). Compound 6 was slightly active against both Escherichia coli DH5 alpha and Micrococcus luteus NRRL B-2618 (diameter halos 8 +/- 2 and 9 +/- 2 mm, respectively). Taxonomically, the amplified 500-bp 16 S rRNA fragment of the Streptomyces sp. DGC1 had 99% identity (BLAST search) to the 16S rRNA gene of Streptomyces atrovirens strain NRRL B-16357. The Journal of Antibiotics (2012) 65, 615-622; doi:10.1038/ja.2012.81; published online 10 October 2012