Marine Drugs· 2026Q1
Derin Deniz Mantarından Elde Edilen Yeni Bileşikler Böbrek Hasarı ve Kanser Üzerinde Umut Vadediyor
Drimane-Pyrone-Type Meroterpenoids and Co-Isolated Compounds from the Deep-Sea Fungus Penicillium rubens MABC05 and Their Anti-Ferroptotic and Cytotoxic Activities
- 0atıf
- Q1SCImago
- 2026yıl
Kısa özet
Derin deniz mantarından elde edilen 17 bileşik arasında altı yeni driman-piron meroterpenoidi ve yeni bir hibrit molekül bulunmaktadır. Bileşik 15, böbrek hasarıyla ilişkili bir hücre ölüm yolu olan ferroptozu 12.8 μM EC50 değeriyle güçlü bir şekilde inhibe etti; bileşikler 11 ve 16 ise sırasıyla 4.3 ve 8.4 μM IC50 değerleriyle meme kanseri hücrelerine karşı sitotoksisite gösterdi.
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Özet (abstract)
Ferroptosis is a critical driver of tubular necrosis, and its effective inhibition holds significant potential for mitigating renal injury. In this study, chemical investigation of the strain Penicillium rubens MABC05 yielded nine drimane-pyrone-type meroterpenoids (1–9), including six previously undescribed analogues, a previously undescribed tetrahydroxanthone-ergosterol hybrid (10), four steroids (11–14), and three xanthone derivatives (15–17). Their structures were elucidated via comprehensive spectroscopic analysis, supported by single-crystal X-ray diffraction (Mo Kα for 1 and 3, and Cu Kα for 6) and 13C NMR calculations (2 and 10). The absolute configurations of 1–5 and 10 were assigned by ECD calculation. Compounds 1–6 represent a rare group of meroterpenoids containing a fused drimane-type sesquiterpene and pyrone skeleton. Additionally, two storage-induced oxidative artifacts of 10 were also characterized. These compounds were evaluated for anti-ferroptotic and cytotoxic activities. Compound 15 exhibited inhibition against RSL3-induced ferroptosis in human renal proximal tubular epithelial cells with an EC50 value of 12.8 μM; it effectively reduced MDA levels, elevated GSH content, and suppressed lipid radical generation. Compounds 11 and 16 exhibited cytotoxicity against MCF-7 cells with IC50 values of 4.3 and 8.4 μM, respectively. Compound 15 represents a promising chemotype for ferroptosis inhibitors with potential for mitigating renal tubular injury.
Yazarların özeti; kaynağından alınmıştır. Marine Drugs, 2026 · DOI ↗
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