Toad venom bufadienolides and bufotoxins: An updated review

Bufadienolides, naturally found in toad venoms having steroid-like structures, reveal antiproliferative effects at low doses. However, their application as anticancer drugs is strongly prevented by their Na+/K+-ATPase binding activities. Although several kinds of research were dedicated to moderating their Na+/K+-ATPase binding activity, still deeper fundamental knowledge is required to bring these findings into medical practice. In this work, we reviewed data related to anticancer activity of bufadienolides such as bufalin, arenobufagin, bufotalin, gamabufotalin, cinobufotalin, and cinobufagin and their derivatives. Bufotoxins, derivatives of bufadienolides containing polar molecules mainly belonging to argininyl residues, are reviewed as well. The established structures of bufotoxins have been compiled into a one-page figure to review their structures. We also highlighted advances in the structure-modification of the structure of compounds in this class. Drug delivery approaches to target these compounds to tumor cells were discussed in one section. The issues related to extraction, identification, and quantification are separated into another section.