p-Terphenyl alcohols from a marine sponge-derived fungus, Aspergillus candidus OUCMDZ-1051

Abstract

In order to discover structurally new and bioactive compounds from marine life, we studied the secondary metabolites of the marine-derived fungi associated with a marine sponge (XS-3) from the Xisha islands. As a result, 4-O-methylcandidusin A (1), a new p-terphenyl alcohol, along with nine known analogs (2-10), were isolated and identified from the marine spongederived fungus Aspergillus candidus OUCMDZ-1051. The structures of these compounds were determined by analyzing spectroscopic data, especially 1D and 2D NMR. The new compound 1 selectively inhibited the growth of the MDA-MB-468, BT474 and A431 human cancer cell lines with the IC 50 values of 1.84, 6.05 and 0.98 μmol/L, respectively. Compound 1 also displayed a selective antimicrobial activity against Escherichia coli with an MIC value of 27.3 μmol/L. The results indicated 4-O-methylcandidusin A (1) as a potential lead in the new drug discovery for triple negative breast cancer, invasive ductal breast cancer and epidermoid cancer. The antimicrobial metabolites also evidenced a clue for chemical defense of sponges by their associated microorganisms.

Marine natural products

“…The Aspergillus genus was once again a source of many new metabolites, including the cyclic heptapeptide unguisin G 319 , 146 aryl-dibenzofuran 320 , 147 azaphilones 321–325 (ref. 148) and chlorinated PKS–NRPS metabolites 326–328 .…”

p-Terphenyls From Aspergillus sp. GZWMJZ-055: Identification, Derivation, Antioxidant and α-Glycosidase Inhibitory Activities

“…In addition, some p-terphenyl derivatives were also total synthesized (Yonezawa et al, 1998;Takahashi et al, 2017;Zhang et al, 2018). As reported, p-terphenyls had a broad spectrum of biological properties, such as cytotoxic (Wang et al, 2019(Wang et al, , 2020, antimicrobial (Intaraudom et al, 2017), and phosphodiesterase inhibitory (El-Elimat et al, 2013) activities, but the most interesting bioactivities were antioxidative (Kuhnert et al, 2015) and αglucosidase inhibitory activities (Ma et al, 2014). Furthermore, p-terphenyls can also be isolated from edible mushroom (Liu et al, 2004;Ma et al, 2014;Wang et al, 2014), indicating that this kind of compounds have low toxicity in the human body and are very suitable for the research of anti-diabetic drugs.…”

“…The fermentation potency (5.3-9.5 g/kg) and the α-glucosidase inhibitory activity (IC 50 15.0 to 2.0 µg/mL) of the ethyl acetate (EtOAc) extracts of the fermentation significantly increased after adding the leaves of Eucommia ulmoides to the culture medium (Figure 1). Chemical investigation led to the isolation of sixteen p-terphenyls, including the new 3-O-methyl-4deoxyterprenin (1) as well as the known 4-deoxyterphenyllin (2) (Lin et al, 2019), 4 -deoxy-2 -methoxyterphenyllin (3) (Shan et al, 2019), 5 -methoxy-[1,1 :4 ,1 -terphenyl]-2 ,3 ,4,4tetraol (4) (Zhang et al, 2018), terphenyllin (5) (Kamigauchi et al, 1998), 3-hydroxyterphyllin (6) (Liu et al, 2012), 3,3dihydroxyterphyllin (7) (Liu et al, 2012), 4 -deoxyterphenyllin (8) (Shan et al, 2019), 4 -deoxy-3-hydroxyterphenyllin (9) (Wang et al, 2020), 3 -O-methylterphenyllin (10) (Yan et al, 2017), 4 -deoxyprenylterphenyllin (11) (Wei et al, 2007), prenylterphenyllin A (12) (Cai et al, 2011), 3-methoxyterprenin (13) (Kamigauchi et al, 1998), 4 -deoxycandidusin A (14) (Guo et al, 2012), candidusin A (15) (Wang et al, 2020), and candidusin B (16) (Liu et al, 2012; Figure 2). Compounds 15 and 16 were also, respectively, prepared from compounds 6 and 7 by an intramolecular oxidative cyclization of air catalyzed by silica gel (Scheme 1).…”

Metabolic Profiling and In Vitro Assessment of the Biological Activities of the Ethyl Acetate Extract of Penicillium chrysogenum “Endozoic of Cliona sp. Marine Sponge” from the Red Sea (Egypt)

“…Marine sponges, which are also known as microbial fermenters, are outstanding sources of highly diverse microbial communities, including new fungal species. The true producers of natural compounds from marine invertebrates are symbiotic microorganisms, which account for approximately 40 percent of the sponge’s volume [ 3 , 4 , 5 ]. The distinct pore structure of the sponges makes them an ideal host for a wide variety of marine microorganisms, which account for a large portion of sponge biomass [ 6 ].…”