Enantioselective inhibitory abilities of enantiomers of notoamides against RANKL-induced formation of multinuclear osteoclasts

Abstract

The marine-derived Aspergillus protuberus MF297-2 and the terrestrial A. amoenus NRRL 35600 produce enantiomeric prenylated indole alkaloids. Investigation of biological activities of the natural and synthetic derivatives revealed that (−)-enantiomers of notoamides A and B, 6-epi-notoamide T, and stephacidin A inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)–induced osteoclastogenic differentiation of murine RAW264 cells more strongly than their respective (+)-enantiomers. Among them, (−)-6-epi-notoamide T was the most potent inhibitor with an IC50 value of 1.7 μM.

Taichunins E–T, Isopimarane Diterpenes and a 20-nor-Isopimarane, from Aspergillus taichungensis (IBT 19404): Structures and Inhibitory Effects on RANKL-Induced Formation of Multinuclear Osteoclasts

“…RAW 264 cells seeded on a six-well plate (2.7 × 10 4 cells/well) were treated with sRANKL (50 ng/mL) and 17 (30 μM) and incubated for 24 h. RNA extraction and real-time RT-PCR analysis were conducted as previously described …”

“…Inhibitors of RANKL-induced formation of multinuclear osteoclasts are seen as promising drug leads in the prevention and treatment of osteoporosis. We screened extracts of marine sponges and fungi by measuring the RANKL-induced upregulation of TRAP activity in RAW264 cells and found several inhibitors from marine sponges − and a fungus . Halenaquinone, a pentacyclic polyketide, from the marine sponge Petrosia alfani inhibited RANKL-induced osteoclastogenesis with an IC 50 value of 2 μM, which is at least a result of suppression of the NF-κB and Akt signaling pathways through inhibition of IκB degradation and Akt phosphorylation, respectively .…”

“…Sipholane-type triterpenes, isolated from the Red Sea marine sponge Siphonochalina siphonella , inhibited RANKL-induced osteoclastogenesis . A series of enantiomeric prenylated indole alkaloids were isolated from the marine-derived Aspergillus protuberus MF297-2 and the terrestrial A. amoenus NRRL 35600, and (−)-enantiomers of notoamides A and B, 6- epi -notoamide T, and stephacidin A inhibited RANKL-induced osteoclastogenesis more potently than their respective (+)-enantiomers . Among these, (−)-6- epi -notoamide T was the most potent inhibitor, with an IC 50 value of 1.7 μM.…”

Marine natural products that inhibit osteoclastogenesis and promote osteoblast differentiation

“…Later, two antipodes, (–)-stephacidin A and (+)-notoamide B, were isolated from the terrestrial fungi A. amoenus NRRL 35,600 [ 33 ]. Biological activities were assessed with natural and synthetic analogues, and a series of the (–)-enantiomers of notoamides A and B, 6- epi -notoamide T, and stephacidin A inhibited RANKL-induced osteoclastogenesis more strongly than their respective (+)-enantiomers [ 34 ]. Among the tested compounds, a synthetic compound (–)-6- epi -notoamide T was the most potent, with an IC 50 value of 1.7 µM.…”

Amakusamine from a Psammocinia sp. Sponge: Isolation, Synthesis, and SAR Study on the Inhibition of RANKL-Induced Formation of Multinuclear Osteoclasts

“…RAW264 cells seeded on a six-well plate (2.7 × 10 4 cells/well) were treated with sRANKL (50 ng/mL) and 1 (30 or 50 μM) and incubated for 24 h. RNA extraction and real-time RT-PCR analysis were conducted as previously described. 25 Cytotoxicity Assay. The cytotoxicity assay was performed with RAW264 cells using MTT.…”