Characterization of three new antiproliferative shikimic acid derivatives and known pyrrolizidine alkaloids from Senecio oleosus guided by diagnostic ions and molecular networking.

内容摘要

The genus Senecio comprises more than 1,200 species, at least 25 of which are known to be toxic due to the presence of pyrrolizidine alkaloids. In Brazil, approximately 68 species occur, predominantly in rural and mountainous regions. This study was performed to investigate the specialized metabolites of Senecio oleosus using isolation and dereplication strategies and to evaluate their antiproliferative activity against tumor cell lines. A phytochemical investigation of S. oleosus was conducted using various chromatographic techniques. Structural elucidation was based on spectroscopic analyses and comparison with literature data. Dereplication was performed using UHPLC-HRMS/MS. Molecular networking was generated through GNPS2 and analyzed using Cytoscape. Antiproliferative activity was assessed using the MTT assay. The study led to the isolation of three new esterified shikimic acid derivatives. Dereplication of pyrrolizidine alkaloids was guided by the diagnostic fragment ions at m/z 120 and m/z 138. Diagnostic ions for esterified shikimic acid derivatives were established based on the fragmentation patterns observed in the MS/MS spectra of the isolated compounds. Molecular networking analysis enabled the annotation of 36 additional putative esterified shikimic acid derivatives. One triesterified shikimic acid derivative exhibited promising antiproliferative activity against the HCT-116 cell line, with an IC50 value of 10.5 µg.mL- 1 (20.2 µM). In total, 82 compounds were identified in S. oleosus. Except for N-oxide retrorsine and N-oxide senecionine, all compounds are reported for the first time in this species. Esterified shikimic acid derivatives emerged as the major group of specialized metabolites in S. oleosus, and triesterified derivatives demonstrated promising antiproliferative activity.