Open AccessBufadienolides from the Eggs of the Toad Bufo bufo gargarizans and Their Antimelanoma Activities
Author(s) -
Shiwen Zhou,
Jing Quan,
Zi Wei Li,
Yong Ge,
Zhuo Shang,
Ze Ping Chen,
Lei Wang,
Xin Yuan Li,
Xiao Qi Zhang,
Jie Li,
Jun Shan Liu,
Hai Yan Tian
Publication year - 2021
Publication title -
journal of natural products
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.976
H-Index - 139
eISSN - 1520-6025
pISSN - 0163-3864
DOI - 10.1021/acs.jnatprod.0c00840
Subject(s) - toad , in vivo , bufo , biological activity , biology , cell culture , cytotoxic t cell , chemistry , in vitro , stereochemistry , biochemistry , endocrinology , genetics
Toads produce potent toxins, named bufadienolides, to defend against their predators. Pharmacological research has revealed that bufadienolides are potential anticancer drugs. In this research, we reported nine bufadienolides from the eggs of the toad Bufo bufo gargarizans , including two new compounds ( 1 and 3 ). The chemical structures of 1 and 3 , as well as of one previously reported semisynthesized compound ( 2 ), were elucidated on the basis of extensive spectroscopic data interpretation, chemical methods, and X-ray diffraction analysis. Compound 1 is an unusual 19-norbufadienolide with rearranged A/B rings. A biological test revealed that compounds 2 and 4 - 8 showed potent cytotoxic activities toward human melanoma cell line SK-MEL-1 with IC 50 values less than 1.0 μM. A preliminary mechanism investigation revealed that the most potent compound, 8 , could induce apoptosis via PARP cleavage, while 5 and 6 significantly suppressed angiogenesis in zebrafish. Furthermore, an in vivo biological study showed that 5 , 6 , and 8 inhibit SK-MEL-1 cell growth significantly.