Secondary Metabolites from the Leather Coral-Derived Fungal Strain Xylaria sp. FM1005 and Their Glycoprotein IIb/IIIa Inhibitory Activity

Abstract

Five new tyrosine derivatives (1−5), one new phenylacetic acid derivative (6), two new quinazolinone analogues (7 and 8), one new naphthalenedicarboxylic acid (9), and one new 3,4-dihydroisocoumarin derivative (10), together with seven known compounds, were isolated from the fungus Xylaria sp. FM1005, which was isolated from Sinularia densa (leather coral) collected in the offshore region of the Big Island, Hawaii. The structures of compounds 1−10 were elucidated by extensive analysis of NMR spectroscopy, HRESIMS, and ECD data. Due to their structure similarity to the antiplatelet drug tirofiban, compounds 1−5 together with 6 were investigated for their antithrombotic activities. Compounds 1 and 2 strongly inhibited the binding of fibrinogen to purified integrin IIIb/IIa in a dose-dependent manner with the IC 50 values of 0.89 and 0.61 μM, respectively, and compounds 1 and 2 did not show any cytotoxicity against A2780 and HEK 293 at 40 μM.

Secondary Metabolites from Coral-Associated Fungi: Source, Chemistry and Bioactivities

“…Two new quinazolinone analogues, namely 4-(7,8-Dihydroxy-4-oxoquinazolin-3(4H)-yl), butanoic acid ( 85 ) and 4-(8-Hydroxy-4-oxoquinazolin-3(4H)-yl) butanoic acid ( 86 ), were isolated from the fungus Xylaria sp. FM1005, which was gathered from a leather coral Sinularia densa found in the area of the Big Island, Hawaii [ 57 ]. Further investigation of Neosartorya laciniosa (KUFC 7896) led to the isolation of a novel tryptoquivaline derivative, tryptoquivaline T ( 87 ) [ 58 ].…”

“…FM1005, namely sinuxylamide A ( 115 ), sinuxylamide B ( 116 ), sinuxylamide C ( 117 ), sinuxylamide D ( 118 ), and assinuxylamide E ( 119 ). Compounds 115 and 116 also showed significant inhibition against the binding of fibrinogen to purified integrin IIIb/IIa in a dose-dependent manner with IC 50 values of 0.89 and 0.61 μM, respectively [ 57 ]. A new compound pseuboydone E ( 120 ) and three described compounds, namely speradine C ( 121 ), 24, 25-dehydro-10,11-dihydro-20-hydro-xyaflavinin ( 122 ), and aflavinine ( 123 ), were found in a fungus associated to Lobophytum crissum .…”

“…Naphthalenedicarboxylic acid ( 288 ), a novel compound, was isolated from the fungus Xylaria sp. FM1005, discovered from Sinularia densa [ 57 ]. The soft-coral-derived fungus Alternaria alternata L3111′A was the source of a new perylenequinone-related compound, alternatone A ( 289 ), and a known perylenequinone named alterperylenol ( 290 ).…”

Sulfur-Containing Compounds from Endophytic Fungi: Sources, Structures and Bioactivities

“…For example, sinuxylamides A and B were obtained from Xylaria sp. FM1005, an endophytic fungus isolated from Sinularia densa (leather coral) collected in the offshore region of the Big Island, Hawaii [ 64 ]. Sinuxylamides A and B showed no antibacterial activity or cytotoxicity at 40 μM, but they strongly inhibited the binding of fibrinogen to purified integrin IIIb/IIa in a dose-dependent manner with IC 50 values of 0.89 and 0.61 μM, respectively.…”

New Alkaloids From a Hawaiian Fungal Strain Aspergillus felis FM324

“…In the past few years, our research group has studied the secondary metabolites of some marine fungi including different Aspergillus species from Hawaii. These secondary metabolites had different types of structures and exhibited various biological activities ( Li et al, 2015 ; Fei-Zhang et al, 2016 ; Li et al, 2016 ; Huang et al, 2017 ; Li et al, 2018 ; Li et al, 2019 ; Wang et al, 2019 ; Zaman et al, 2020a ; Wang et al, 2020 ; Zaman et al, 2021 ). In our continuing search for bioactive molecules from Hawaiian fungi, we studied an extract of Aspergillus felis FM324, which led to the separation and identification of ten compounds (1–10).…”