論文 - 詳細
| RRC ID | 85371 |
|---|---|
| 著者 | Elgahamy AA, El-Desoky AH, Otify AM, El Fishawy AM, El-Beih AA. |
| タイトル | Molecular networking derived from untargeted LC-MS/MS analysis to discover inhibitors of RANKL-induced osteoclastogenesis from Egyptian marine sponge-associated fungi. |
| ジャーナル | Sci Rep |
| Abstract |
In continuous search for RANKL induced osteoclastogenesis inhibitors, twenty-six fungal isolates were obtained from ten Red Sea marine sponges collected from Egypt and the ethyl acetate fractions of their cultures' methanol extracts were assessed in RAW264 macrophages. Active fractions were profiled via LC-MS/MS, followed by untargeted molecular networking, leading to the tentative identification of eight unreported compounds (1, A2, C1, C2, C4-C7), and thirteen known compounds. The two active fungi were identified and deposited in GenBank with accession numbers PQ423742 and PQ423748 for Aspergillus flavus and Cladosporium colombiae, respectively. Bioassay-guided isolation afforded two bisphenol diglycidic ethers, 1 and 2, and two diketopiperazines, 3 and 4 from A. flavus, while C. colombiae yielded cinnamic acid (5), two diketopiperazines (6 and 7), and altenuene (8). Structures were elucidated by NMR and mass spectroscopic analyses, which revealed 1 to be isolated for the first time from natural sources. Isolated compounds were biologically evaluated. Only 1 and 8 inhibited RANKL-induced formation of mature multinucleated osteoclasts with IC50 57.14 and 38.35 µM, respectively, without cytotoxicity against RAW264 macrophages. The ADMET properties for 1 and 8 were predicated using SwissADME and pkCMS platforms. 8 showed superior solubility and lower toxicity than compound 1. |
| 巻・号 | 15(1) |
| ページ | 27137 |
| 公開日 | 2025-7-25 |
| DOI | 10.1038/s41598-025-12456-y |
| PII | 10.1038/s41598-025-12456-y |
| PMID | 40715314 |
| PMC | PMC12297304 |
| MeSH | Animals Chromatography, Liquid Egypt Fungi* / chemistry Fungi* / isolation & purification Liquid Chromatography-Mass Spectrometry Macrophages / drug effects Mice Osteoclasts* / cytology Osteoclasts* / drug effects Osteoclasts* / metabolism Osteogenesis* / drug effects Porifera* / microbiology RANK Ligand* / metabolism RANK Ligand* / pharmacology RAW 264.7 Cells Tandem Mass Spectrometry |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |