Prenylated Indole Diketopiperazines from the Marine-Derived Fungus Aspergillus versicolor

Abstract

Seven new prenylated indole diketopiperazines, versicamides A-G (1-7) and a novel chemical derivative from 7, versicamide H (8), along with three known analogic diketopiperazines (9-11) were obtained from the marine-derived fungus Aspergillus versicolor HDN08-60. Their structures were determined by spectroscopic techniques, including 2D NMR, ECD calculations, and single-crystal X-ray diffraction analysis, together with the assistance of further chemical conversions. The cytotoxicities of 1-8 were tested against the HeLa, HCT-116, HL-60, and K562 cell lines, but only 8 exhibited moderate activity against HL-60 cells, with an IC50 value of 8.7 μM. Further investigation with target screening showed that 8 exhibited selective PTK inhibitory activities.

Characterization of Aspergillus fumigatus Isolates from Air and Surfaces of the International Space Station

“…A chemical database (Reaxys) search using the proposed formula revealed no known A. fumigatus metabolite that matched this formula. However, the metabolites versicamide F from Aspergillus versicolor (37) and taichunamides C and F from Aspergillus taichungensis (38) matched the proposed formula. These findings might indicate that the compound is a previously uncharacterized prenylated indole alkaloid produced by A. fumigatus .…”

Recent Discovery of Heterocyclic Alkaloids from Marine-Derived Aspergillus Species

“…SF-5976 obtained from an unidentified marine organism that was collected in the Ross Sea [41]. Compounds 46-51 were identified as six new prenylated indole diketopiperazines and they were isolated from a culture of the marine sediment-derived fungus A. versicolor HDN08-60 [42]. These compounds are characterized by a 6/6/5/8/6/5 hexacyclic ring system that possesses a hydrogenated azocine unit.…”

“…Structurally, compound 57 possesses an unprecedented skeleton of a 2,5-dihydro-1H-azepino [4,3-b]quinoline system, while 58 contains a novel 6/6/11/6/5 pentacyclic ring system. Moreover, the former compound is considered to be a derivative of the latter [42]. Figure 3 lists the structures of quinazoline alkaloids that are produced by marine-derived Aspergillus species.…”

“…Marine-derived fungi could be isolated from every possible marine habitat, such as marine sediments, marine invertebrates (sponges, corals, ascidians, and holothurians), and vertebrates (mainly fish), as well as marine plants (algae, driftwood, and mangrove plants) [74,75]. As shown in Table 1 [46,56,64], while the other strains were collected from marine sediments at depths above 100 m or even tideland mud [28,35,36,40,42,57,65,69,70]. Unfortunately, the source of the producing strain of 31-35 (A. sulphureus KMM 4640 and I. felina KMM 4639) was not described [39].…”

Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines

“…The 2‐dimethyl‐3‐methyl‐azetidine ring on 1 is fused to the HPI moiety, which is unprecedented in nature and is challenging to construct by chemical synthesis. The azocine ring can be found in some natural products, such as cycloechinulins and versicamides …”