Albanitriles A-G: Antiprotozoal Polyacetylene Nitriles from a Mycale Marine Sponge Samuele Sala, † Jane Fromont, ‡ Oliver Gomez, ‡ Daniel Vuong, § Ernest Lacey, § and Gavin R. Flematti* ,† † School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia ‡ Western Australian Museum, Welshpool, WA 6106, Australia § Microbial Screening Technologies Pty. Ltd., Smithfield, NSW 2164, Australia * S Supporting Information ABSTRACT: Seven new nitrile-bearing polyacetylenes, named albani- triles A-G, were isolated from a marine sponge of the Mycale genus (Order: Poecilosclerida, Family: Mycalidae) collected near Albany, Western Australia. Structural elucidation was achieved using a combination of high-resolution mass spectrometry and ultraviolet/ visible, infrared, and nuclear magnetic resonance spectroscopy. The compounds were found to possess moderate activity against Giardia duodenalis when compared to a metronidazole positive control. M arine sponges are a constant source of novel compounds, many with interesting biological activities. 1 As part of our ongoing chemical investigation into Western Australian marine species, seven new nitrile-bearing poly- acetylenic secondary metabolites named albanitriles A-G(1- 7) were isolated from a marine sponge of the Mycale genus, which currently remains uncharacterized at the species level. 2 Compounds containing conjugated alkyne systems, commonly referred to as polyacetylenes, form a significant class of secondary metabolites, often exhibiting a range of bioactivities including anticancer, antibacterial, and antifungal activity. 3-5 Over 2000 polyacetylene natural products have been identified from terrestrial and marine sources, most notably from members of the Asteraceae family of plants and from marine sponges of the Petrosia genus. 5,6 Despite the scarcity of nitrile functional groups within the natural products literature, 7 the Mycale genus has furnished two compound families with nitrile functionalities: these are the fatty acid derived mycalenitriles, 8-11 and the nucleic acid derived mycalisines A and B. 12 In addition, natural products containing cyanohydrin functional groups, present on com- pounds 3 and 7, remain underreported from either marine or terrestrial sources. 7,13,14 Cytotoxic and antibiotic secondary metabolites have also been isolated from Mycale marine sponges, notably the peloruside macrolides, 15, 16 as well as the mycalamide alkaloids 17 and the mycapolyols. 18 Testing of compounds 1- 4 against a panel of microorganisms and cell lines revealed the metabolites had minor antibacterial activity and moderate antiprotozoal activity against Giardia duodenalis, the parasite responsible for Giardiasis. 19 The isolation, structure assign- ment, and biological activities of 1-7 are reported herein. ■ RESULTS AND DISCUSSION Initial high-performance liquid chromatography (HPLC)- photodiode array screening of a Mycale sp. MeOH/CH 2 Cl 2 (1:1) extract revealed the presence of several major lipophilic compounds with a series of UV absorbance peaks and troughs reminiscent of conjugated polyacetylene systems. 20 Large-scale (25.6 g) extraction of the sponge and isolation of the desired compounds via semipreparative HPLC yielded compounds 1- 7 in quantities sufficient for structural characterization. High-resolution mass spectrometry (HRMS) analysis of the purified compound 1 revealed a molecular formula consistent with C 18 H 20 N 2 . The calculated molecular formula represented a highly unsaturated molecule possessing a double bond equivalence of 10, suggesting a high level of conjugation. Aromatic moieties were considered unlikely due to the absence of typical signals in the 1 H NMR spectrum (Table 1). As the compound contained two nitrogen atoms, twin nitrile groups (double bond equivalent (DBE) of 4) were hypothesized as a possible means of reconciling the calculated DBE of the compound with a nonaromatic system. The nitrile hypothesis was supported by an IR signal at 2215 cm -1 and confirmed by two resonances observed by 13 C NMR spectroscopy (δ C 119.3 Received: September 3, 2019 Article pubs.acs.org/jnp Cite This: J. Nat. Prod. XXXX, XXX, XXX-XXX © XXXX American Chemical Society and American Society of Pharmacognosy A DOI: 10.1021/acs.jnatprod.9b00840 J. Nat. Prod. XXXX, XXX, XXX-XXX Downloaded via UNIV OF CALIFORNIA SANTA BARBARA on December 14, 2019 at 04:54:47 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.