Molecular Networking Reveals Indolo-Sesquiterpene Hybrids from the Marine-Derived Fungus Aspergillus terreus 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, Aspergillus terreus N4-9, was investigated by using molecular networking strategies. The known indolo-sesquiterpene hybrid terreuside B (1) along with three new analogues, terreusides C–E (2–4), were targeted isolation from the fungal cultures. Additionally, three putative new congeners, terreusides F–H (8–10), 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 2 demonstrated significant growth inhibitory activity against human gastric cancer SGC-7901 cells with an IC₅₀ value of 6.25 μM.