Polyketide Skeletons from the Marine Alga‐Derived Fungus Coniothyrium cereale

Abstract

The fungus Coniothyrium cereale was isolated from the Baltic Sea alga Enteromorpha sp. Upon cultivation in saline medium, C. cereale produced the structurally unprecedented isoindole pseudoalkaloid conioimide (1) and the polyketide cereoanhydride (2). Because of the very limited amount of compounds isolated, the structures of 1 and 2 were established from extensive NMR spectroscopic and mass spectrometric analyses, and in the case of 1, the structural analysis was completed by NMR shielding calculations. Conioimide and cereoanhydride represent new structural types of polyketides. Experiments with 13C‐labeled acetate proved the polyketide nature of the major and known C. cereale metabolite (–)‐trypethelone (3), which is proposed to be the precursor of cereoanhydride. Conioimide has prominent and selective inhibitory activity towards the protease human leukocyte elastase (HLE), an enzyme involved in many inflammatory diseases, with an IC50 (half maximal inhibitory concentration) value of 0.2 μg mL–1.

Mycochemistry of marine algicolous fungi

“…Among these, myrothenone A (343) significantly inhibited tyrosinase with an IC 50 value of 6.6 μM, which is more potent than kojic acid used currently for personal care (Li et al 2005). Compound 345 showed scavenging activity against DPPH radicals with an IC 50 value of 8.4 μM (Li et al 2006a), and 353-355 selectively inhibited HLE with IC 50 values of 3.01, 9.28, and 0.7 μM, respectively (Elsebai et al 2011b(Elsebai et al , 2012. The cytotoxicity of 356 was illustrated by its effect on L-6 rat skeletal muscle myoblast cells with an MIC value of 3.7 μg/mL and 1 μM), which also exhibited antiplasmodial activity against two strains (K1 and NF54) of Plasmodium falciparum with IC 50 values of 736 and 378 ng/mL (1.72 and 0.88 μM), respectively, and inhibited Trypanosoma cruzi with an MIC value of 1.1 μg/mL (Osterhage et al 2000).…”

Marine Compounds and Cancer

“…Gogos (1998) [139] carried out a randomized prospective study with patients with solid tumors who received fish oil supplementation; patients treated with -3 PUFA had an increased immunomodulating effect and prolonged survival.…”

“…However, anticancer and cancer preventive activities of the polysaccharides from marine animals have been studied insufficiently. Polysaccharide SEP isolated from the eggs of the sea urchin Strongylocentrotus nudus effectively inhibited the growth of S180 tumor and the hepatocellular carcinoma in vivo via the activation of lymphocytes and macrophages, amplification of B and T cell proliferation, and increased secretion of such cytokines as IL-2, TNF-and IFN- [138][139][140][141]. The sulfated polysaccharide conjugate from viscera of abalone Heliotis discus hannai, administered at doses of 1-40 mg/kg to mice inhibited tumor growth and increased lymphocyte proliferation, as well as natural killer cell activity and antibody production.…”

“…Isoindole pseudoalkaloid conioimide (118, Figure 28) and the polyketide cereoanhydride (119, Figure 28) were isolated from the fungus Coniothyrium cereale isolated from the Baltic Sea alga Enteromorpha sp. Conioimide has prominent and selective inhibitory activity towards the protease human leukocyte elastase (HLE), an enzyme involved in many inflammatory diseases, with an IC50 value of 0.2 g/mL, whereas cereoanhydride showed weaker inhibition (IC50 = 16 g/mL) [139]. A ubiquinone derivative, pseudoalteromone A (120, Figure 28), possessing a 9C nor-monoterpenoid moiety, and a 15C compound, pseudoalteromone B (121, Figure 28), were obtained from the marine bacterium Pseudoalteromonas sp.…”

Marine Low Molecular Weight Natural Products as Potential Cancer Preventive Compounds

“…Conioimide has prominent and selective inhibitory activity towards the protease human leukocyte elastase (HLE), an enzyme involved in many inflammatory diseases, with an IC 50 value of 0.2 μg/mL, whereas cereoanhydride showed weaker inhibition (IC 50 = 16 μg/mL) [139]. …”