Combined prioritization and dereplication-based rapid identification of new 8-alkylated coumarins: podurins A and B from the leaves of Murraya paniculata and cytotoxic evaluation

Abstract

Profiling extracts using LC-HRMS is now a standard and powerful method to search for new metabolites for drug discovery. LC-HRMS generates a long list of mass (m/z) values, and identifying the known metabolites by matching the mass values with a database is a common strategy of conventional dereplication. The current manuscript describes the peak prioritization strategy to target new metabolites from a vast mass list. The peak prioritization strategy resulted in the identification of two previously undescribed coumarins along with the known metabolites. The identified new metabolites were taken on priority for isolation and characterization. New metabolites were characterized as 8-alkylated coumarin, podurin A (1), and podurin B (2), along with known coumarins, mexoticin (3), vanillin (4), and acacetin (5). NMR and single-crystal X-ray crystallography established the structure of the metabolites. The isolated compounds were assessed for their cytotoxic potential against human adenocarcinoma cell lines. The IC₅₀ of compounds 1–3 is 103.9 μM, 159.7 μM, and 170.3 μM, respectively.