Molecular Networking Reveals Indolo-Sesquiterpene Hybrids from the Marine-Derived Fungus <i>Aspergillus terreus</i> N4‑9

Tandem mass spectrometry (MS/MS)-based molecular networking has emerged as a powerful tool for rapid dereplication of known compounds and discovery of novel structural analogues within the same metabolite class. In this study, the chemical diversity of indolo-sesquiterpene hybrids from the mangrove rhizosphere soil-derived fungus, <i>Aspergillus terreus</i> N4-9, was investigated by using molecular networking strategies. The known indolo-sesquiterpene hybrid terreuside B (<b>1</b>) along with three new analogues, terreusides C–E (<b>2</b>–<b>4</b>), were targeted isolation from the fungal cultures. Additionally, three putative new congeners, terreusides F–H (<b>8</b>–<b>10</b>), were tentatively identified through systematic analysis of their characteristic MS/MS fragmentation patterns. Detailed fragmentation studies revealed two predominant cleavage pathways for these hybrids related to fracture of the methylene bridge connecting Rings A and B (Type I) and furan opening in Ring C (Type II). Compound <b>2</b> demonstrated significant growth inhibitory activity against human gastric cancer SGC-7901 cells with an IC₅₀ value of 6.25 μM.