Indimicins A-E, Bisindole Alkaloids from the Deep-Sea-Derived Streptomyces sp. SCSIO 03032 Wenjun Zhang, † Liang Ma, † Sumei Li, † Zhong Liu, ‡ Yuchan Chen, § Haibo Zhang, † Guangtao Zhang, † Qingbo Zhang, † Xinpeng Tian, † Chengshan Yuan, † Si Zhang, † Weimin Zhang, § and Changsheng Zhang* ,† † CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Materia Medica, Collaborative Innovation Center of Deep Sea Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, People’s Republic of China ‡ Guangzhoujinan Biomedicine Research and Development Center, Guangdong Key Laboratory of Bioengineering Medicine, Jinan University, 601 West Huangpu Road, Guangzhou 510632, People’s Republic of China § Guangdong Institute of Microbiology, 100 Central Xianlie Road, Guangzhou 510070, People’s Republic of China * S Supporting Information ABSTRACT: Five new bisindole alkaloids, indimicins A-E (1-5), bearing a unique 1′,3′-dimethyl-2′-hydroindole moiety, were isolated from the marine-derived Streptomyces sp. SCSIO 03032, along with two new compounds, lynamicins F and G (6 and 7). Their planar structures were elucidated by detailed interpretation of their MS and NMR spectroscopic data, and the absolute configurations were determined by X-ray crystallographic analysis (for 1), comparison of CD spectra (for 2-4), and quantum chemical calculations (for 5). Indimicin B (2) exhibited moderate cytotoxic activity toward the MCF-7 cell line. B isindole alkaloids are a large family of natural products with diverse biological activities that have attracted pharmaceut- ical interest. 1 Several analogues of bisindole alkaloids have been used as protein kinase inhibitors and DNA-topoisomerase I inhibitors in cancer clinical trials. 2 Although hundreds of family members of bisindole alkaloids that are derived from the fusion of two molecules of L-tryptophan have been reported, 1 their chemical space is continuing to be expanded by isolation from natural sources, 3 chemical synthesis, 4 biosynthesis and metabolic engineering, 5 and the culture-independent approach of meta- genomic screening. 6 In accordance with the emerging importance of marine actinomycetes in offering opportunities for the discovery of novel natural products, 7 new bisindole alkaloids with unique bioactivities have been reported from marine-derived actinomycetes. 8 Recently, we also reported the isolation of spiroindimicins, new bisindole alkaloids with unprecedented [5,6] or [5,5] spiro-rings, from the deep-sea- derived actinomycete Streptomyces sp. SCSIO 03032, 9 which is also capable of producing lynamicins, 9 α-pyridone antibiotic piericidins, 10 and polyketide macrolactam heronamides. 11 A careful investigation of the production profile of Streptomyces sp. SCSIO 03032 reveals the presence of several minor components with characteristic UV spectra of bisindole alkaloids. Herein we report the isolation and biological activity of five new bisindole analogues, indimicins A-E(1-5), bearing a unique 1′,3′-dimethyl-2′-hydroindole, together with two new bisindole alkaloids, lynamicins F (6) and G (7). ■ RESULTS AND DISCUSSION The deep-sea-derived strain Streptomyces sp. SCSIO 03032 has been previously shown to produce spiroindimicins A-D, 9 lynamycins A and D, 9 and piericidins, 10 when cultivated in the modified A1BFe + C medium. 9,12 An investigation of metabolite Received: April 28, 2014 Published: July 28, 2014 Article pubs.acs.org/jnp © 2014 American Chemical Society and American Society of Pharmacognosy 1887 dx.doi.org/10.1021/np500362p | J. Nat. Prod. 2014, 77, 1887-1892