New Oxazole-bearing Secondary Metabolites from Marine Derived Streptomyces sp.

Abstract

Actinobacterial strains were selectively isolated from marine mud flat samples collected in the intertidal zone of Anmyeon island in Korea. Chemical profiling of these strains by LC/MS identified that the strain AH05, which belongs to the genus Streptomyces based on its 16S rDNA sequence, produced two compounds showing distinct UV spectra with λmax at 231 and 276 nm. The planar structures of the compounds, 669A and B, were determined as new members of the oxazolomycin family bearing a spiro-β-lactone-γ-lactam motif and an oxaole moiety by 1D and 2D NMR data. The relative configurations were assigned by ROESY and J-based configuration analysis. The absolute configurations were determined by the modified Moshers method. The major compound 669A inhibited breast cancer (MCF7), lung cancer (A549), and gastric cancer (SNU638) cell lines in an SRB assay.

안면도의 토양 샘플로부터 방선균의 LC/MS 분석을 통해 231 nm, 276 nm에서 뚜렷한 UV 스펙트럼을 가지며 옥사졸을 포함한 화합물을 발견하였다. 순수하게 분리한 두 물질은 옥사졸로마이신으로 알려진 물질의 새로운 유도체였으며, 옥사졸 부분에 메틸화가 이루어진 물질들이었다. 입체구조는 ROESY NMR 분석 및 화학 반응에 의해 결정되었고, SRB 실험을 진행한 결과 유방암 (MCF-7), 폐암 (A549), 위암 (SNU638) 세포를 억제하는 항암효과를 보였으며, 그 중에서도 유방암 세포주 (MCF-7, T47D)에서 특이적이면서 높은 활성이 나타났다. 이러한 결과는 기존의 옥사졸로마이신 유도체들에서는 발견되지 않았다. 그 외에도 항염, 결핵균에 대한 활성을 나타내었다.