Austalides, Osteoclast Differentiation Inhibitors from a Marine-Derived Strain of the Fungus Penicillium rudallense

Abstract

Four new meroterpenoids, austalides V−X (1−3) and a farnesylated phthalide derivative (4), were isolated from the culture of the marine fungus Penicillium rudallense, together with eight known meroterpenoids derivatives (5−12). Their structures, including absolute configurations, were determined by spectroscopic methods. All of the isolated compounds were evaluated for their inhibitory activities on the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation. Compounds 1, 2, 5−7, and 10 exhibited potent osteoclast differentiation inhibitory activity with ED 50 values of 1.9−2.8 μM.

Highly Substituted Phenol Derivatives with Nitric Oxide Inhibitory Activities from the Deep-Sea-Derived Fungus Trichobotrys effuse FS524

“…In summary, six new highly substituted phenol derivatives, trieffusols A-F (1-6), along with eleven known analogs (7)(8)(9)(10)(11)(12)(13)(14)(15)(16), were identified from the deep-sea-derived fungus Trichobotrys effuse FS524. Interestingly, trieffusols A and B share an intriguing 6-6/6/6 tetracyclic ring system with the formation of an unprecedented ploy-substituted 9-phenyl-hexahydroxanthone skeleton, which is often encountered as one of the most ubiquitous and intriguing functional moieties in the pharmaceutical drugs but rarely discovered in natural products.…”

“…In terms of pharmacological research, secondary metabolites derived from marine fungi are increasingly recognized as important sources of biologically meaningful natural products [8,9]. These MNPs have exhibited a wide range of biological activities such as anti-cancer [10], fungicidal [11], pro-angiogenic [12], anti-lymphangiogenic [13], and osteoclast differentiation inhibitory activities [14].…”

“…Herein, we present the isolation, structure elucidation, and biological evaluation of them in this study. activities [14]. Therefore, in-depth chemical research on the MNPs would pave the way to providing potential model structures and precursor drugs for new drug developments.…”

“…Therefore, in-depth chemical research on the MNPs would pave the way to providing potential model structures and precursor drugs for new drug developments. During our continuing research for structurally unique and biologically significant NPs from marine fungi [15][16][17], the fungus strain Trichobotrys effuse FS524, isolated from a sediment sample collecting at the South China Sea, attracted our attention, and chemical investigation of the strain resulted in the isolation of six new highly substituted phenol derivatives, trieffusols A-F (1-6), along with eleven known analogues ( Figure 1), including phomalone (7) [18], 2,4-dihydroxy-3-(2-hydroxyethyl)-6-methoxyphenyl)-3-hydroxybutan-1-one (8) [18], (E)-1-(2,4-dihydroxy-3-(2-hydroxyethyl)-6-methoxyphenyl)but-2-en-1-one (9) [18], deoxyphomalone (10) [18], phomalichenone A (11) [18], methylindole-3-acetate (12) [19], 3-indole acetic acid (13) [20], 4-methoxyphenylacetic acid (14) [21], papuline (15) [22], and stigmast-4-en-3-one (16) [23]. Furthermore, their structures with absolute configurations were successfully established with the aid of spectroscopic data analyses, single-crystal X-ray diffraction experiments, and ECD calculations.…”

Terpenoids from the Deep-Sea-Derived Fungus Penicillium thomii YPGA3 and Their Bioactivities

“…These meroterpenoids were mainly produced by the species of the fungal genera Aspergillus and Penicillium, especially those from marine environments. Since austalides A−E were first reported in 1981, a total of 36 analogues have been identified [2][3][4][5][6][7][8][9][10][11]. The structural variations of austalides are attributed to oxidation occurring at C-13, C-14, C-17, and the isopropyl (C-15, C-25, C-26) to generate alcohol, isopropenyl, lactone, ester, or ether functionalities.…”