Mycoleptodiscins A and B, Cytotoxic Alkaloids from the Endophytic Fungus Mycoleptodiscus sp. F0194 Humberto E. Ortega, † Paul R. Graupner, ‡ Yumi Asai, § Karen TenDyke, ⊥ Dayong Qiu, ⊥ Young Yongchun Shen, ⊥ Nivia Rios, ∥ A. Elizabeth Arnold, Δ Phyllis D. Coley, O,# Thomas A. Kursar, O,# William H. Gerwick, □ and Luis Cubilla-Rios* ,†,# † Laboratory of Tropical Bioorganic Chemistry, Faculty of Natural, Exact Science and Technology, University of Panama, Panama ‡ Natural Products Discovery, Dow AgroSciences, 9330 Zionsville Road, Indianapolis, Indiana 46268, United States § Eisai Co., Ltd., Tsukuba, Ibaraki 300-2635, Japan ⊥ Eisai Inc., 4 Corporate Drive, Andover, Massachusetts 01810, United States ∥ Department of Microbiology, University of Panama, Panama Δ School of Plant Sciences, The University of Arizona, Tucson, Arizona, United States O Department of Biology, University of Utah, Salt Lake City, Utah, United States # Smithsonian Tropical Research Institute, Panama City, Panama □ Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093, United States * S Supporting Information ABSTRACT: Two novel reddish-orange alkaloids, mycolep- todiscin A (1) and mycoleptodiscin B (2), were isolated from liquid cultures of the endophytic fungus Mycoleptodiscus sp. that had been isolated from Desmotes incomparabilis in Panama. Elucidation of their structures was accomplished using 1D and 2D NMR spectroscopy in combination with IR spectroscopic and MS data. These compounds are indole- terpenes with a new skeleton uncommon in nature. Mycoleptodiscin B (2) was active in inhibiting the growth of cancer cell lines with IC 50 values in the range 0.60−0.78 μM. T he International Cooperative Biodiversity Group Program in Panama (ICBG-Panama) has been investigating cytotoxic, antiparasitic, and antimicrobial agents from various natural sources such as marine organisms and endophytic fungi. 1 Tropical endophytic fungi have been demonstrated to be rich and reliable sources of biologically active and chemically novel compounds. 2 Hence, examination of the unique constituents of endophytic fungi from endemic plants collected in Panama’s protected areas is one of our major thrusts. Two hundred and thirty-seven endophytic fungi were isolated from the endemic plant Desmotes incomparabilis (Rutaceae), collected in Coiba National Park, Veraguas, Panama, by Alicia Ibañ ez (STRI, Panama City). Because it showed high biological activity in prescreening assays, the fungus Mycoleptodiscus sp. F0194 was chosen for additional study. In this paper we describe the isolation and structural elucidation of two novel reddish-orange alkaloids, which we have named mycoleptodiscin A (1) and mycoleptodiscin B (2). Compound 1 was obtained as a reddish-orange solid. The molecular formula C 23 H 29 O 2 N was determined by HRESIMS (m/z 352.2277 [M + H] + ). The 1 H NMR spectrum showed four methyl singlets [δ H 0.89 (H-20), 0.91 (H-19), 1.09 (H-21) and 1.28 (H-18)] and a number of multiplets between 2.2 and 1.3 ppm. The DEPT135 spectrum showed six aliphatic methylenes [δ C 18.8 (C-3), 19.6 (C-11), 19.6 (C-7), 38.3 (C-12), 41.3 (C-6), and 42.9 (C-8)] and two methines [δ C 57.4 (C-10) and 57.9 (C-4)]. These provided evidence of the terpenoid moiety of 1. When the 1 H NMR spectrum of 1 was obtained in chloroform, a signal was observed at 9.4 ppm, consistent with the proton of a secondary amine. HMBC correlations from a methine singlet at δ H 7.00 (H-2) to δ C 125.0 (C-2a), 131.7 (C- Received: November 13, 2012 Published: April 5, 2013 Note pubs.acs.org/jnp © 2013 American Chemical Society and American Society of Pharmacognosy 741 dx.doi.org/10.1021/np300792t | J. Nat. Prod. 2013, 76, 741−744