Integrated experimental and computational characterization of bioactive metabolites from Streptomyces paradoxus GH53 with antimicrobial, antioxidant, and antitumor activities
Streptomyces species are widely recognized as valuable sources of secondary metabolites with diverse biological activities. In this study, the isolate GH53 was identified as Streptomyces paradoxus based on morphological characteristics and partial 16 S rRNA gene sequence analysis. Fermentation conditions were optimized to enhance metabolite production, and the crude ethyl acetate extract was chemically characterized using GC-MS, FT-IR, and UV-Vis spectroscopy. The analytical profile suggested the presence of a chemically complex mixture containing fatty acids, fatty acid derivatives, hydrocarbons, and terpenoid-related constituents. The IC₅₀ values of the crude extract were 0.175 ± 0.013 and 0.097 ± 0.006 mg/mL for the DPPH and ABTS radical scavenging assays, respectively. Because the calculated DPPH IC₅₀ value was slightly below the lowest tested concentration, it should be interpreted as a fitted estimate derived from the dose–response curve rather than as a directly measured concentration point. It also showed cytotoxic activity against HePG-2 and MCF-7 cell lines, with IC₅₀ values of 19.50 ± 1.5 and 28.81 ± 2.0 µg/mL, respectively. To provide a preliminary molecular interpretation of these extract-level bioactivities, selected representative metabolites tentatively identified by GC-MS were evaluated individually as defined ligands using molecular docking, molecular dynamics simulation, and ADMET prediction. The modeled compounds showed favorable predicted interactions with selected antimicrobial-, antioxidant-, and anticancer-related protein targets, and the corresponding protein–ligand complexes generally maintained stable interaction profiles during simulation. However, ADMET analysis indicated potential limitations for some high-molecular-weight lipophilic constituents, including poor drug-likeness, limited predicted solubility, and possible toxicity liabilities. Overall, these findings suggest that S. paradoxus GH53 represents a promising source of bioactive metabolites for future fractionation, purification, structural confirmation, and compound-level biological evaluation. The results should be interpreted as preliminary screening evidence and not as confirmation of therapeutic efficacy or direct systemic drug suitability.