Asperindoles A–D and a p-Terphenyl Derivative from the Ascidian-Derived Fungus Aspergillus sp. KMM 4676

Abstract

Four new indole-diterpene alkaloids asperindoles A–D (1–4) and the known p-terphenyl derivative 3″-hydroxyterphenyllin (5) were isolated from the marine-derived strain of the fungus Aspergillus sp., associated with an unidentified colonial ascidian. The structures of 1–5 were established by 2D NMR and HRESIMS data. The absolute configurations of all stereocenters of 1–4 were determined by the combination of ROESY data, coupling constants analysis, and biogenetic considerations. Asperindoles C and D contain a 2-hydroxyisobutyric acid (2-HIBA) residue, rarely found in natural compounds. Asperindole A exhibits cytotoxic activity against hormone therapy-resistant PC-3 and 22Rv1, as well as hormone therapy-sensitive human prostate cancer cells, and induces apoptosis in these cells at low-micromolar concentrations.

Recent Discovery of Heterocyclic Alkaloids from Marine-Derived Aspergillus Species

“…This compound was able to induce the apoptosis of 22Rv1 cells at low micromolar concentrations. Cell cycle progression analyses of 22Rv1 cells that were treated with 12 also revealed discrete G2/M-phase arrest [29]. Compound 18 exhibited potent cytotoxic activity against HL-60 and LNCap cells with IC 50 values of 3.1 and 4.9 µM, respectively, but with no significant cytotoxicity against the rest of the tested cell lines (HepG2, Hela, A375, A549, HT29, SK-BR-3, and MCF-7) [31].…”

“…Compounds 12-15 were isolated from the fungal strain Aspergillus sp. from an unidentified colonial ascidian and then characterized as four new indole-diterpene alkaloids [29]. Compounds 16 and 17 were isolated and identified from the cultures of the endophytic fungus A. nidulans EN-330 that were collected from the marine red alga Polysiphonia scopulorum [30].…”

“…Z-4) residing in the marine isopod Ligia oceanica [37,[51][52][53], while only one heterocyclic alkaloid (130) was identified from the endophytic fungi obtained from the marine crab Xenograpsus testudinatus [71]. Moreover, the producing strains of 21, 22, and 54-56 originated from marine shrimp or prawns [34,45], while those of compounds 12-15 were derived from an unidentified colonial ascidian that was collected at Shikotan Island in the Pacific Ocean [29]. In addition to these producing strains of marine invertebrate origin, only one fungal strain, which produced 84-91, was obtained from the marine fish Mugil cephalus, representing vertebrates [50].…”

Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts

“…KMM 4676 is associated with an unidentified ascidian from Shikotan Island [151]. A new alkaloid, asperindole A, produced by this fungus, exhibits cytotoxic activity against hormone therapy-resistant cancer cells and induces apoptosis [151]. The specificity of fungal communities has been discovered in the ascidian Eudistoma vannamei, in which the fungus Aspergillus sp.…”

One New Terphenyl Glycoside From a Sponge-Derived Fungus Trichoderma reesei (HN-2016-018)

“…collected from an unknown colonial ascidian. 16 Aspergillus candidus IF10 obtained from marine environment produced 3 new terphenyls, 4-deoxy-isoterprenin, 4-de-oxyprenylterphenyllin, and prenyl-terphenyllin, exhibiting strong cytotoxic activities. 17 As a part of our current investigation on exploring for new marine natural bioactive products, 5 pterphenyl glycosides were isolated from a coral derived-fungus Aspergillus candidus.…”