In Silico, In Vitro, and In Vivo Biological Activities of Thiol Compounds Isolated from Sperm and Eggs of Sea Urchins

Background: Thiol compounds are made up of sulfur-containing amino acids and thiohistidine derivatives. It has generated attention for its diverse biological activities. Aim: The goal of this study is to isolate, characterize, and detect the biological activities, molecular docking, toxicity, and histopathological alterations of thiol compounds isolated from sea urchins. Methods: The chemical structure of thiol compounds extracted from the eggs and sperm of sea urchins was verified using elemental analysis, IR, MS, and NMR spectroscopy. In vitro tests include cytotoxicity, anticancer assay, antioxidant, cell migration, anti-inflammatory, and antimicrobial assays. The OECD Guideline 423 was followed when conducting the in vivo toxicity investigation. Results: The chemical formulas for Ovo thiol A and Sperm thiol are C7H11N3O2S and C6H8N3O2S. Ovo thiol A and Sperm thiol exhibited no cytotoxicity to normal HSF cells (IC50 > 1000 µg/mL). However, against MCF-7 cancer cells, Ovo thiol A showed potent anticancer activity (IC50 = 17.35 µg/mL), and Sperm thiol exhibited significant activity (IC50 = 22.25 µg/mL). Ovo thiol A demonstrated higher antioxidant and anti-inflammatory activity than Sperm thiol. No significant antimicrobial or wound healing activities were observed. Docking results indicated favorable interactions of both Ovo thiol A and Sperm thiol with Bcl-2, Keap1, and glycogen synthase kinase-3β. Computational ADME studies predicted favorable oral passive absorption for Ovo thiol A in humans, while Sperm thiol showed low gastrointestinal absorption. In vivo toxicity assessment revealed non-significant changes in liver and kidney biomarkers. Also, the histology of the liver and kidney of mice treated with thiol compounds showed normal structure. Discussion: The biological activities of Ovo Thiol A and Sperm Thiol are related to the unique position of the thiol group in their structure. Conclusion: Ovo thiol A (1-N-Methyl-4-mercaptohistidine) and Sperm thiol (4- mercaptohistidine) are safe chemicals with biological activity such as anticancer, antioxidant, and anti-inflammatory properties, paving the way for their usage in medical applications.