Antiangiogenic Metabolites from a Marine-Derived Fungus, Hypocrea vinosa

Abstract

The aims of this study were to investigate the role of tyrosine kinase in intracellular signaling and to search for lead compounds with tyrosine kinase inhibitory activity from metabolites of marine-derived fungi. We initially prepared 400 extracts from 200 species of marine fungi and then subjected them to a tyrosine kinase screening assay using human umbilical vein endothelial cell lysate. Tyrosine kinase inhibitory activity was observed among certain metabolites of Hypocrea vinosa. We isolated one known compound, SC2051 (1), as well as two new compounds, hypochromins A (2) and B (3), which have a bis(naphtho-gamma-pyrone) skeleton. Compounds 1-3 showed tyrosine kinase inhibitory activity, with IC(50) values of 42.1, 58.7, and 18.0 microMu, respectively. Furthermore, compounds 1-3 exhibited inhibitory effects on proliferation, migration, and tubule formation.

Unusual dimeric tetrahydroxanthone derivatives from Aspergillus lentulus and the determination of their axial chiralities

“…The CD Exciton Chirality method has been applied to some axially chiral determinations before, such as those of binaphthyl, biarylic dihydronaphthopyranone3031, and bis(naphtho- γ -pyrone)32. However, a very few exceptions were reported due to their complicated chromophores and non-negligible intense magnetic transition dipole moments3334.…”

Bis-naphtho-γ-pyrones from Fungi and Their Bioactivities

“…In addition to the cytotoxic, antitumor and antimicrobial activities of bis-nathphtho-γ-pyrones mentioned above, other biological activities include tyrosine kinase inhibition [23], HIV-1 integrase inhibition [3], calmodulin-sensitive cycle nucleotide phosphodiestease inhibition [22], triacylglycerol synthesis inhibition [14], xanthine oxidase inhibition [31], acyl-CoA:cholesterol acyltransferase inhibition [4], central nerveous system depressant effects [42], immunological activity [12], botulinum neutotoxin serotype A inhibition [57], drug resistance-reversing activity [58], and Taq DNA polymerase inhibition [30], which are outlined in Table 5. Anti-tubercular activity [7] …”

“…The remaining bis-naphtho-γ-pyrones produced by fungi and their bioactivities need to be further studied. In recent years, an increasing number of bis-naphtho-γ-pyrones have been isolated from endophytic fungi [3,10,20] and marine-derived fungi [7,16,23]. These fungi could be the rich sources of biologically active metabolites that are indispensable for medicinal and agricultural applications [1,[63][64][65][66].…”

Fungal Endosymbionts of Seaweeds

“…These metabolites exhibit anticancer, antibacterial, antiplasmodial, anti-inflammatory, nematicidal, antiviral and antiangiogenic activities (Bhadury et al 2006;Newman and Hill 2006;Bhatnagar and Kim 2010;Ohkawa et al 2010). Marine-derived fungi associated with marine algae have been reported to produce novel metabolites including aromatic polyketides (Pontius et al 2008), alkaloids (Tsuda et al 2004), sesquiterpenes (Bugni and Ireland 2004) and terpenes (Klemke et al 2004;K€ onig et al 2006;L€ osgen et al 2007).…”