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• W2896881890 abstract "Pentacyclic triterpenoid acids (PCTTAs) are pleiotropic agents that target many macromolecular end-points with low to moderate affinity. To explore the biological space associated with PCTTAs, we have investigated the carboxylate-to-hydroxamate transformation, discovering that it de-emphasizes affinity for the transcription factors targeted by the natural compounds (NF-κB, STAT3, Nrf2, TGR5) and selectively induces inhibitory activity on HIF prolyl hydrolases (PHDs). Activity was reversible, isoform-selective, dependent on the hydroxamate location, and negligible when this group was replaced by other chelating elements or O-alkylated. The hydroxamate of betulinic acid (5b) was selected for further studies, and evaluation of its effect on HIF-1α expression under normal and hypoxic conditions qualified it as a promising lead structure for the discovery of new candidates in the realm of neuroprotection." @default.
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• W2896881890 date "2018-10-10" @default.
• W2896881890 modified "2023-09-28" @default.
• W2896881890 title "Triterpenoid Hydroxamates as HIF Prolyl Hydrolase Inhibitors" @default.
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• W2896881890 doi "https://doi.org/10.1021/acs.jnatprod.8b00514" @default.
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