Abstract
Five new ergostanes, penicisteroids D−H (1−5), were isolated from the liquid culture of the deep-sea-derived fungus Penicillium granulatum MCCC 3A00475, along with 27 known compounds. The structures of the new steroids were established mainly on the basis of extensive analysis of 1D and 2D NMR as well as HRESIMS data. Moreover, the absolute configurations of 1 were confirmed unambiguously by the single-crystal X-ray crystallography. Compounds 2 and 4–7 showed moderate antiproliferative effects selectively against 12 different cancer cell lines with IC50 values of around 5 μM. Compounds 2 and 6, potent RXRα binders with Kd values of 13.8 and 12.9 μM, respectively, could induce apoptosis by a Retinoid X Receptor (RXR)-α-dependent mechanism by regulating RXRα transcriptional expression and promoting the poly-ADP-ribose polymerase (PARP) cleavage. Moreover, they could inhibit proliferation by cell cycle arrest at the G0/G1 phase.
Highlights
Retinoid X receptor-α (RXRα), one of the most promising members of the nuclear receptor superfamily, plays an important role for the treatment of cancer, metabolic, and neurodegenerative diseases [1,2,3,4]
15.9 trans-relationship between them were established by the large half-peak-width of
Transfected dual-luciferase reporter and PG5 were treated with RXRα ligand 9-cis-Retinoic acid (9-cis, 0.1 μM), RXRα antagonist 3-[4-Hydroxy-3-[5,6,7,8[5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-(pentyloxy)-2-naphthalenyl]phenyl]-2-propenoic acid
Summary
Retinoid X receptor-α (RXRα), one of the most promising members of the nuclear receptor superfamily, plays an important role for the treatment of cancer, metabolic, and neurodegenerative diseases [1,2,3,4]. It can form heterodimers with retinoic acid retinoid (RAR), thyroid hormone receptor (TR), nerve growth factor-induced gene B (NGFIB), etc. Compounds) strategy,Interestingly, the fungus was subjected to further investigation using medium, different different fermentation conditions. We report the isolation, structure elucidation, and cytotoxicity againstby a cell cycle arrest. Cytotoxicity against a panel of cancer cell lines of these compounds.
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