文摘
In addition to known compounds, the leaves of Vernonia amygdalina afforded the new sesquiterpene lactones 14-O-methylvernolide (<b>2b>), 3鈥?deoxyvernodalol (<b>6b>), and vernomygdalin (<b>8b>). These and related compounds were evaluated for modulation of a series of thiol trapping-sensitive transcription factors (NF-魏B, STAT3, and Nrf2), involved in the maintenance of the chronic inflammatory condition typical of human degenerative diseases. Vernolide (<b>1b>) emerged as a potent inhibitor of STAT3 and NF-魏B and showed cytostatic activity toward the prostate cancer cell line DU45, arresting the cell cycle at the S phase. The exomethylene lactones are characterized by multiple Michael acceptor sites, as exemplified by vernolide (<b>1b>) and vernodalol (<b>5b>). By using the nuclear magnetic resonance-based cysteamine assay, the most reactive thiophilic site could be identified in both compounds, and competitive experiments qualified vernolide (<b>1b>) as being more thiophilic than vernodalol (<b>5b>), in agreement with the results of the pharmacological assays.