Toad venom bufadienolides and bufotoxins: An updated review

Abstract

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.

Comprehensive Analysis of Bufadienolide and Protein Profiles of Gland Secretions from Medicinal Bufo Species

“…The fragment ions at m / z 175 indicated the loss of diacid and the retention of arginine fragments according to previous reports [ 18 , 19 ]. And, the ions at m / z 156 and 170 were identified as the L-histidines and L-1-methylhistidines cleaved from the diacid-conjugated histidine esters [ 3 ], respectively.…”

“…Due to its potent clinical efficacy, in-depth chemical and pharmacological research have been conducted on TV, particularly focusing on two types of micro-molecular components: bufadienolides and indole alkaloids. Over 140 bufadienolides and indole alkaloids have been identified from Bufo species, along with sterols and amino acids [ 2 , 3 ]. Additionally, increasing attention has started being paid to the functional proteins and peptides in TV, and a series of active macromolecular components have been identified, including proteins with anti-inflammatory, analgesic, antioxidant, catalytic, and transport activities [ 4 , 5 , 6 ] as well as polypeptides associated with antitumor and antimicrobial properties [ 7 , 8 ].…”

Diastereodivergent Synthesis of A-Ring Lactones Derived from Cholesterol and Diosgenin: A Convenient Solution for an Old Problem – NMR and X-ray Characterization

“…), 3.29 (dd, J = 3.0, 3.0 Hz, H-5), 0.79 (s, H-19); -anomer 5.33 (dd J = 3.3 Hz, 1H, H-3 -eq), 3.83 (dd, J = 2.9, 2.9 Hz, 1H), 0.83 (s, H-19); Shared signals. 4.40 (m, 1H, H-16), 3.47 (ddd, J = 11.2, 4.7, 1.9 Hz, 1H, H-26 eq), 3.37 (dd, J = 10.9, 10.9 Hz, 1H, H-26 ax. ), 0.96 (d, J = 6.9 Hz, 3H, H-21), 0.78 (d, J = 6.3 Hz, 3H, H-27), 0.76 (s, 3H, H-18).…”

“…Lactones are secondary metabolites found in living organisms of both marine and terrestrial kingdoms, that due to their versatility as synthetic intermediates as well as their wide spectrum of biological activities, have concentrated a great deal of attention. 1 Steroid lactones constitute a subfamily that includes several naturally occurring bioactive members like Brassinolide (1), 2 Bufalin (2) 3 and Digitoxigenin (3). 4 A wide variety of synthetic derivatives that includes bioactive compounds like Dropinerone (4) 5 Spironolactone (5) 6 and Testolactone (6) 7 amongst many others, 8 has been also reported (Figure 1).…”

CS-6-Induced p62 Accumulation Exacerbates DNA Damage: A Mechanistic Insight into Colorectal Cancer Suppression

“…Several animal-derived substances, including Cinobufagin [25] and Lytta vesicatoria [26], have exhibited potential anti-tumor properties. Among them, Gamabufotalin (CS-6) is a bufodienolactone comprising 1.76-4.97% of toad venom, a traditional Chinese medicine derived from dried toad skin and parotid venom [27,28]. Studies have unveiled the e cacy of CS-6 against various malignant tumors, including glioblastoma[18], non-small cell lung cancer [29], and breast cancer [30].…”