From Chemical Defense to Drug Discovery: Bioactive Molecules, Pharmacological Activities, and Therapeutic Potential of Rhaebo guttatus and Rhinella marina Secretions.

Amazonian bufonid toads represent an important source of bioactive compounds with promising pharmacological potential. Among them, Rhaebo guttatus and Rhinella marina produce complex cutaneous and parotoid gland secretions composed mainly of bufadienolides, indole alkaloids, antimicrobial peptides, biogenic amines, and other secondary metabolites that play essential roles in chemical defense. This narrative review summarizes current knowledge regarding the ecology, chemical composition, biological activities, toxicological profile, and therapeutic potential of secretions from these two Amazonian species. A literature search was conducted using PubMed, Scopus, Web of Science, SciELO, and Google Scholar, covering publications from 2005 to 2025. The reviewed evidence demonstrates that these secretions exhibit a broad spectrum of biological activities, including antiproliferative, antimicrobial, antiparasitic, antiviral, immunomodulatory, antioxidant, anti-inflammatory, analgesic, and larvicidal effects. These pharmacological properties are primarily associated with the modulation of molecular targets such as Na+/K+-ATPase, intracellular signaling pathways, oxidative stress, and inflammatory mediators. Despite their remarkable therapeutic potential, the clinical application of crude secretions remains limited by their significant systemic toxicity and narrow therapeutic window. Overall, the secretions of R. guttatus and R. marina constitute a valuable natural reservoir of bioactive molecules with considerable potential for drug discovery and the development of innovative therapeutic agents.