Isolation of two new terpeptin analogs—JBIR-81 and JBIR-82—from a seaweed-derived fungus, Aspergillus sp. SpD081030G1f1

Abstract

The marine environment has recently been described as a source of novel chemical diversity for drug discovery, as many bioactive substances are isolated from marine organisms, including phytoplankton, algae, sponges, tunicates and mollusks. 1 Our group has reported the isolation of azaspiracid-22 2 and JBIR-44 3 from marine sponges. Microorganisms from marine habitats, especially fungi, 4 also constitute a promising untapped resource for discovering novel bioactive substances such as diketopiperazine alkaloids, 5 trichodermatides 6 and carbonarones. 7 We also have reported new sesquiterpenes-JBIR-27 and JBIR-28-from a tunicate-derived fungus Penicillium sp. SS080624SCf1, 8 a new aspochracin derivative-JBIR-15-from a marine spongederived fungus Aspergillus sclerotiorum Huber Sp080903f04, 9 and new glycosyl benzenediols-JBIR-37 and JBIR-38-from a marine spongederived fungus, Acremonium sp. SpF080624G1f01. 10 Further investigation resulted in the discovery of two new terpeptin analogs, designated as JBIR-81 (1) and JBIR-82 (2), together with terpeptin 11 (3), from the culture of a marine-derived Aspergillus sp. SpD081030G1f1 ( Figure 1a). This paper describes the fermentation, isolation, structure elucidation, and in brief, the biological activity of 1 and 2.The fungus, Aspergillus sp. SpD081030G1f1, was isolated from a seaweed, Sargassum sp., collected at the sea shore of Ishigaki Island, Okinawa Prefecture, Japan. The strain was cultivated in 50-ml test tubes containing 15 ml of the seed medium (24 g l -1 potato dextrose broth, BD Biosciences, San Jose, CA, USA). The test tubes were shaken on a reciprocal shaker (355 r.p.m.) at 27 1C for 3 days. Aliquots (5 ml) of the seed culture were inoculated into 500-ml Erlenmeyer flasks containing 9 g oatmeal (Quaker, Chicago, IL, USA), 30 ml vegetable juice (KAGOME, Nagoya, Japan) and incubated at 27 1C for 14 days in static culture.The solid culture (20 flasks) was extracted with 80% aqueous acetone (400 ml). The extract was evaporated in vacuo, and the residual aqueous concentrate was partitioned with EtOAc (100 mlÂ3). After drying over Na 2 SO 4 , the EtOAc layer was evaporated. The dried residue (845 mg) was subjected to normal-phase medium-pressure liquid chromatography (Purif-Pack SI-60, Moritex, Tokyo, Japan) using a CHCl 3 -MeOH stepwise solvent system (0, 5 and 10% MeOH). The fractions containing 1-3 were collected by HPLC-MS monitoring. The target eluate (5% MeOH, 28 mg) was further purified by preparative reverse-phase HPLC using an L-column 2 ODS column (20 i.d.Â150 mm; Chemical Evaluation and Research Institute, Tokyo, Japan) with a 2996 photodiode array detector (Waters, Milford, MA, USA) and a 3100 mass detector (Waters) developed using 25% aqueous MeOH containing 0.1% formic acid (flow rate, 10 ml min À1 ) to yield 1 (1.1 mg, retention time (Rt) 9.7 min), 2 (1.4 mg, Rt 21.4 min) and 3 (2.0 mg, Rt 19.2 min).Compounds 1 The presence of an amide group was deduced from their IR spectra (n max (KBr) 3315, 1631 cm À1 for 1; and 3313, 1631 cm À1 for 2). The UV sp...

Secondary Metabolites from the Marine Algal-Derived Endophytic Fungi: Chemical Diversity and Biological Activity

“…SpD081030G1f1 (isolated from the brown alga Sargassum sp., collected from the sea shore of Ishigaki Island, Okinawa Prefecture, Japan). Both metabolites were strong radical scavengers due to theie protective effect against L-glutamate toxicity (with EC 50 values of 0.7 and 1.5 µM) [69]. Two new indoloditerpene derivatives, asporyzins A (145) and B (146), and one new congener, asporyzin C (147), were obtained from the endophytic fungus Aspergillus oryzae cf-2, which was isolated from the marine red alga Heterosiphonia japonica (Yantai, China).…”

“…Ten new sesquiterpenoids, isosativenetriol(69), drechslerines A (70) and B (71), 9-hydroxyhelminthosporol (72), drechslerines C-G(73)(74)(75)(76)(77), and sativene epoxide (78) (l "Fig. 2), were isolated from a culture of the fungus Drechslera dematioidea from the inner tissue of the marine red alga Liagora viscida (Mediterranean Sea).…”

Marine Indole Alkaloids

“…We will make use of Pelletier’s general definition of 1983, according to which alkaloids are “cyclic organic compounds containing nitrogen in a negative oxidation state which are of limited distribution among living organisms” [ 2 ]. As an additional demarcation against the world of peptides, polypeptidic structures and macrocyclic peptides derived from tryptophan, such as terpeptins [ 3 ] and related structures [ 4 ], milnamides [ 5 , 6 ], diazonamides [ 7 ], lucentamycin B [ 8 ], pipestelides [ 9 ], kahalalides [ 10 , 11 , 12 ], jaspamides [ 13 ], jasplakinolides [ 14 ], etc. , will not be discussed here.…”

Bioactive secondary metabolites from endophytes and associated marine derived fungi

“…The free radical scavenging activities of the compounds were evaluated by testing the protective activity against L-glutamate toxicity in N18-RE-105 cells. Compounds 100-102 showed strong protective activity against L-glutamate toxicity in cells with IC 50 values of 0.7, 1.5 and 0.9μM, respectively, compared to that observed for α-tocopherol, a representative anti-oxidant (IC 50 8.8μM) (Izumikawa et al 2010).…”