Bioactive Peptides from Caudate Amphibians: Synthesis and Assessment of Antioxidant and Antimicrobial Activities

Natural products represent a growing class of bioactive compounds with significant therapeutic relevance in modern drug discovery. Especially peptides gained growing attention in pharmaceutical research due to their biological potency, selectivity, and synthetic accessibility. Among these, amphibian skin secretions were recognized as a rich source of bioactive peptides. In this study, we report the synthesis and analysis of the antioxidant and antimicrobial bioactivities of peptides derived from the skin of caudate amphibians, a largely underexplored group in peptide-based drug discovery. Seven caudate amphibian skin peptides, namely salamandrin-I (<b>1</b>), tylotoin (<b>2</b>), ramosin (<b>3</b>), CCK-TV (<b>4</b>), andricin-I (<b>5</b>), Ad-Cath (<b>6</b>), and infraim-I (<b>7</b>) were synthesized by solid-phase peptide synthesis and analytically characterized. Their antioxidant potential was assessed using a radical scavenging assay, while antimicrobial efficacy was evaluated against Gram-positive and Gram-negative bacterial strains as well as yeast as a fungal representative. Finally, their structural features were analyzed by molecular dynamics simulations and circular dichroism spectroscopy. Salamandrin-I and CCK-TV exerted the strongest antioxidant potential, while salamandrin-I and ramosin showed distinct antimicrobial activities. These results highlight the therapeutic potential of caudate amphibian peptides as scaffolds for novel bioactive compounds in natural product-based drug discovery.