Molecular Networking-Guided Discovery of Phenolic Constituents from Fruits of Mallotus philippinensis

The fruits of Mallotus philippinensis are an underexplored source of chemically diverse and biologically active natural products, previously reported to exhibit anti-inflammatory, antiviral, and cytotoxic activities. In this study, ion identity molecular networking (IIMN) resulted in the discovery of four previously undescribed phenolic derivatives (runakamalas A-D (1-4)), together with the known compounds mallotophilippen F (5), 3',4'-dihydroxyrottlerin (6), and 4'-hydroxyrottlerin (7). Their structures were elucidated by HRESIQTOF-MS, MS/MS fragmentation analysis, and NMR spectroscopy. The absolute configurations of 1 and 2 were clarified by vibrational circular dichroism (VCD) spectroscopy supported by quantum-chemical calculations, while the enantiomers of racemic 3 were separated by chiral-phase HPLC, and their absolute configurations were determined by a comparison of experimental and TDDFT-calculated ECD spectra. Among the new isolates, 4 is distinguished by a linear C-8-C-1'-C-4' chain, an unusual structural feature compared with other phloroglucinol derivatives reported from this species. In addition, the structure of compound 5 was confirmed. All isolated compounds were evaluated for their cytotoxicity against the human neuroblastoma SH-SY5Y cell line and for their antioxidant activity using the DPPH radical scavenging assay.