Volatilome Profiling and Apoptosis-sensitizing potential of secondary metabolites from Trichoderma lixii: Integrating GC–MS, Bioassays, and In Silico Docking Approaches

Purpose Trichoderma species are common soil-dwelling fungi that are well known for their extensive production of secondary metabolites, antagonistic qualities against phytopathogens, are remarkable ecological adaptability. Method By a thorough molecular and chemical analysis, a novel isolate known as Trichoderma sp. (TR5) was carefully characterized in this study. Pairwise ITS comparison identified TR5 as Trichoderma lixii and its phylogenetic analysis based on ITS rDNA sequences. The GC MS analysis primarily had contained fatty acids, alkenes, esters, and phthalates Results The most noticeable zones of inhibition was detected by T.lixii derived metabolites against pathogenic bacteria namely Pseudomonas aeruginosa (34.5 mm) and Bacillus cereus (27.4 mm). Additionally, they showed strong antioxidant properties and selective cytotoxicity in a variety of cancer cell lines, with HepG2 cells showing the strongest inhibitory effect (IC ₅₀ =29.01 3.33 µg/ml). IC ₅₀ values of 54.2 µg/ml for DPPH and 149. µg/ml for ABTS assays. Docking suggested favorable interactions of representative VOCs with apoptosis-relevant targets (IKKβ, topoisomerase IIα, β-tubulin, Bcl-2 family), and ADMET predictions indicated acceptable oral bioavailability with low toxicity liabilities. Integrating post hoc prioritization, cyclopentadecanol emerged as the more promising hit - predicted active across several cancer panels and blood - brain barrier permeable. In contrast, N -benzyloxy carbonyl-L-tyrosine exhibited drug-like ADME and strong protein contacts but was predicted inactive across cancer panels. Conclusion Overall TR5 is confirmed to be T. lixii and its volatilome provides a tractable source of apoptosis sensitizing leads. With multifaced biological applications the potential fungi based extracellular metabolites may serve as a potential candidate in pharmaceutical industries.