Antiproliferative Illudalane Sesquiterpenes from the Marine Sediment Ascomycete Aspergillus oryzae

Abstract

The new asperorlactone (1), along with the known illudalane sesquiterpene echinolactone D (2), two known pyrones, 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (3) and its acetate 4, and 4-hydroxybenzaldehyde (5), were isolated from a culture of Aspergillus oryzae, collected from Red Sea marine sediments. The structure of asperorlactone (1) was elucidated by HR-ESIMS, 1D, and 2D NMR, and a comparison between experimental and DFT calculated electronic circular dichroism (ECD) spectra. This is the first report of illudalane sesquiterpenoids from Aspergillus fungi and, more in general, from ascomycetes. Asperorlactone (1) exhibited antiproliferative activity against human lung, liver, and breast carcinoma cell lines, with IC50 values < 100 µM. All the isolated compounds were also evaluated for their toxicity using the zebrafish embryo model.

Antimicrobial Activity of Dihydroisocoumarin Isolated from Wadi Lajab Sediment-Derived Fungus Penicillium chrysogenum: In Vitro and In Silico Study

“…The experimental procedures used in this study were reported previously [ 38 , 39 ]. The 1 H, 13 C NMR and 2D NMR spectra were recorded on a Bruker AMX-700 spectrometer with tetramethylsilane (TMS) as an internal standard.…”

“…The fungal strain was recognized as Penicillium chrysogenum (GenBank accession No. MH127462), according to DNA amplification sequencing of the fungal ITS region, as reported before [ 38 , 39 , 40 , 41 ].…”

Marine natural products

“…144 Other Aspergillus strains were the source of viomellein derivatives 308 and 309, 145 polyketides 310 and 311 (the latter a known synthetic derivative but new NP), 146 156 and sesquiterpenoid lactone 335. 157 Aspergillus oryzae, isolated from a Red Sea sediment, yielded asporychalasin 336, a cytochalasin with a 6/6/11 skeleton. 158 Aspergillus strains derived from so corals were the source of cyclic hexapeptides 337-339, 159 lipodepsipeptide 340, 159 2pyrone derivatives 341 and 342, cyclopentenone derivative 343 and austocystin derivative 344.…”

Research Advances of Bioactive Sesquiterpenoids Isolated from Marine-Derived Aspergillus sp.

“…Orfali et al [ 27 ] first discovered two illudalane sesquiterpenes, asperorlactone ( 41 ) and echinolactone D ( 42 ), from marine sediment ascomycete Aspergillus oryzae , in which compound 41 has an absolute configuration of (5R). Compounds 41 and 42 showed antiproliferative activity against human lung cancer (A549), liver cancer (HepG2), and breast cancer (MCF-7) cell lines, with half maximal inhibitory concentration (IC 50 ) values of asperorlactone ( 41 ) <100 µM.…”

“…According to this report, Orfali et al speculated a biosynthetic pathway of asperorlactone ( 41 ), in which illudol was a key intermediate. The iluane-type sesquiterpene asperorlactone can be synthesized by dehydration, oxidation, and four-membered ring opening [ 27 ].…”