The total synthesis of nocarbenzoxazoles
F (1) and
G (2), originally obtained from the marine-derived halophilic
bacterial strain Nocardiopsis lucentensis DSM 44048,
was achieved via a simple and versatile route involving microwave-assisted
construction of a benzoxazole skeleton, followed by carbon–carbon
bond formation with the corresponding aryl bromides. Unfortunately,
the 1H and 13C NMR spectra of natural nocarbenzoxazole
G did not agree with those of the synthesized compound. In particular,
the spectra of the isolated and synthesized compounds showed considerable
differences in the signals from the protons and carbons in the aryl
group. The revised structure was validated by the total synthesis
of the actual nocarbenzoxazole G (8c) molecule, which
is a regioisomer of the compound that was reported earlier as nocarbenzoxazole
G. The synthesized derivatives showed specific cytotoxicity to the
human cervical carcinoma cell line, HeLa, but did not have any remarkable
effect on the other cell lines.
Although cisplatin is the standard platinum-based anticancer drug used to treat various solid tumors, it can cause damage in normal kidney cells. Protective strategies against cisplatin-induced nephrotoxicity are, therefore, clinically important and urgently required. To address this challenge, we investigated the renoprotective effects of Hypoxylon
truncatum, a ball-shaped wood-rotting fungus. Chemical investigation of the active fraction from the methanol extract of H.
truncatum resulted in the isolation and identification of the renoprotective compounds, hypoxylonol C and F, which ameliorated cisplatin-induced nephrotoxicity to approximately 80% of the control value at 5 μM. The mechanism of this effect was further investigated using hypoxylonol F, which showed a protective effect at the lowest concentration. Upregulated phosphorylation of p38, extracellular signal-regulated kinases, and c-Jun N-terminal kinases following cisplatin treatment were markedly decreased after pre-treatment with hypoxylonol F. In addition, the protein expression level of cleaved caspase-3 was significantly reduced after co-treatment with hypoxylonol F. These results show that blocking the mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of hypoxylonol F isolated from H.
truncatum fruiting bodies.
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