Isolation, Structural Elucidation, and Biological Evaluation of Pyrrole-Based Alkaloids from Sea Anemone-Associated Streptomyces sp. S1502

Three new pyrrole alkaloids, streptopyrroles D-F (<b>1</b>-<b>3</b>), along with four known analogs (<b>4</b>-<b>7</b>) were isolated from Sea Anemone-Associated <i>Streptomyces</i> sp. S1502 via an OSMAC (One Strain Many Compounds)-based strategy. Their structures were elucidated through comprehensive spectroscopic analyses, including HRESIMS and 1D/2D NMR experiments (COSY, HSQC, and HMBC), and further confirmed by X-ray crystallography. Biological evaluation identified streptopyrrole (<b>4</b>) as an anti-MRSA (methicillin-resistant <i>Staphylococcus aureus</i>) agent, while <b>4</b> and <b>6</b> displayed broad-spectrum cytotoxicity and good selectivity against a panel of human cancer cell lines. Notably, <b>4</b> and <b>6</b> showed particularly potent activity against the lung cancer cell lines H1299, SW1573, and A549, with IC₅₀ values ranging from 5.43 to 16.24 μM. Further mechanistic investigation revealed that both compounds suppress the proliferation of lung cancer cells by inducing cell cycle arrest at the G₀/G₁ phase and impair metastatic potential by inhibiting migration and invasion. These findings not only expand the structural diversity of marine-derived pyrrole alkaloids but also reveal the anticancer mechanisms of <b>4</b> and <b>6</b>, highlighting their promise as active candidates for further antitumor drug development, particularly in lung cancer.