Marilines A–C: Novel Phthalimidines from the Sponge‐Derived Fungus Stachylidium sp.

Abstract

A marine-derived fungus of the genus Stachylidium was isolated from the sponge Callyspongia cf. C. flammea. Chemical investigation of the bioactive fungal extract led to the isolation of the novel phthalimidine derivatives marilines A(1) (1a), A(2) (1b), B (2), and C (3). The absolute configurations of the enantiomeric compounds 1a and 1b were assigned by a combination of experimental circular dichroism (CD) investigations and quantum chemical CD calculations. The skeleton of marilines is most unusual, and its biosynthesis is suggested to require uncommon biochemical reactions in fungal secondary metabolism. Both enantiomers, marilines A(1) (1a) and A(2) (1b), inhibited human leukocyte elastase (HLE) with an IC(50) value of 0.86 μM.

Aβ-42 lowering agents from the marine-derived fungus Dichotomomyces cejpii

“…From this fungus recently several indoloditerpenes with activity against methicillin-resistant Staphylococcus aureus [10] and at GPR18 and cannabinoid receptors have been isolated [11]. 16-O-desmethylasporyergosterol-ß-Dmannoside (2) and xanthocillin X dimethyl ether (4) reduced Aβ-42 production in Aftin-5 treated cells. …”

“…A promising source for new secondary metabolites are organisms isolated from unusual, to date little investigated habitats, e.g. marine-derived fungi and bacteria [1][2][3]. Alzheimer"s disease (AD) causes dementia in many elderly people and is an increasing problem, especially in aging western societies [4].…”

Time-Dependent Production of the Bioactive Peptides Endolides A and B and the Polyketide Mariline A from the Sponge-Derived Fungus Stachylidium bicolor 293K04

“…The sponge-derived fungus S. bicolor 293K04 also produces the unprecedented bioactive polyketide-like phthalimidine and phthalide derivatives, marilines (Figure 1), marilones, maristachones, cyclomarinone and marilactone. Their biosynthesis was suggested to require unique and/or rare reactions in fungal secondary metabolism, such as the methylation of the acetate starter unit of the phthalidmidine/phthalide core structure, or the hydroxycyclopentenone ring biosynthesis of cyclomarinone, predicted to be a new carbon arrangement among polyketides [8][9][10]. These polyketides exhibited potent bioactivity in several bioassays, with mariline A1/A2 enantiomers exhibiting human leucocyte elastase inhibition (HLE) with an IC50 of 0.86 μM, as well as antiproliferative activity against cancer cells, antiplasmodial activity, and antagonistic activity against several psychoactive receptors [9].…”

“…These polyketides exhibited potent bioactivity in several bioassays, with mariline A1/A2 enantiomers exhibiting human leucocyte elastase inhibition (HLE) with an IC50 of 0.86 μM, as well as antiproliferative activity against cancer cells, antiplasmodial activity, and antagonistic activity against several psychoactive receptors [9]. [3] and Mariline A1/A2 (3) [9].…”

“…Thus, optimized liquid scaled-up fungal fermentations are needed to progress the lead compound. Furthermore, a 40-day fungal cultivation using 10-L solid media in Fernbach flask format permitted the isolation of a large amount of peptides endolide A and B [3] and a minimal amount of the polyketides marilines A1/A2, marilones A and C [9,10]. Interestingly, an experimental 60-day 10 L solid cultivation of the fungus yielded low amounts of the peptidic endolides, but increased amounts of polyketides mariline A1/A2 (3-fold) or marilone A (8-fold), and seven new polyketides found exclusively in the extracts of the 60-days cultivations [8][9][10] which we reason was an unusually delayed stage of polyketide production.…”