Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 32 4 2026 10 31 Ergostane and Gorgastane Sterols Isolated from Soft Coral: Sarcophyton tenuispiculatum Thomson & Dean. with their Antibacterial, Anti-Biofilm, and Anti-Efflux Pump Activity Against Colistin-Resistant acinetobacter Baumannii Bacteria 566 579 10.34172/ps.43968 EN Samin Mousavi https://orcid.org/0009-0001-0830-4901 Afsaneh Yegdaneh https://orcid.org/0000-0002-8294-1132 Arezoo Mirzaei Hajar Sirous Mohammad Bagher Majnooni Melika Nazemi Mustafa Ghanadian https://orcid.org/0000-0001-6446-4734 Journal Article 10.34172/ps.43968 2026 04 02 2026 06 08 Introduction: Soft corals are increasingly recognized for their antimicrobial potential. Acinetobacter baumannii, an opportunistic pathogen linked to pneumonia and urinary tract infections, often shows resistance to conventional therapies, including colistin. This resistance highlights the urgent need for novel agents with antibacterial and anti-biofilm properties. This study investigated the phytochemical composition and biological activities of steroids isolated from Sarcophyton tenuispiculatum, focusing on antibacterial, anti-biofilm, and efflux pump inhibitory effects against colistin-resistant A. baumannii. Soft coral specimens were collected from Larak Island, Iran, and subjected to phytochemical and biological evaluation, integrating experimental assays with molecular docking and ADMET analyses. Methods: Bioactive metabolites were isolated by solvent partitioning, chromatography, and HPLC. Structures were characterized using NMR and GC-MS. Antibacterial, antibiofilm, and efflux pump inhibitory activities were assessed by MIC, diffusion, crystal violet, cartwheel, and qRT-PCR assays. Docking studies examined MexB binding, while ADMET predictions evaluated pharmacokinetics. Results: Four steroids were identified: gorgosta-5-en-3β-ol(1), ergosta-5-en-3β-ol(2), ergosterol peroxide (3), and 5,8-epidioxy-ergosta-6-en-3-ol(4). Compounds 1–3 reduced biofilm formation (79%, 78%, 62%). Compound 1 showed strong efflux pump inhibition (MIC 500 μg/mL, P<0.001) and, with compound 2, downregulated MexB gene expression. Docking revealed high binding affinities for compounds 1 and 2, comparable to the co-crystallized ligand. ADMET analysis indicated favorable pharmacokinetics for compounds 1 and 2, while compounds 3 and 4 showed mutagenic risks. Conclusion: Steroids 1–3 displayed antibacterial and anti-biofilm activity against colistin-resistant A. baumannii. Compound 1 demonstrated the most promising profile, combining efflux pump inhibition, gene downregulation, and favorable pharmacokinetics, supporting its potential as a lead candidate for drug development.