TY - JOUR
T1 - Bufadienolides from the Eggs of the Toad Bufo bufo gargarizans and Their Antimelanoma Activities
AU - Zhou, Shi Wen
AU - Quan, Jing Yu
AU - Li, Zi Wei
AU - Ye, Ge
AU - Shang, Zhuo
AU - Chen, Ze Ping
AU - Wang, Lei
AU - Li, Xin Yuan
AU - Zhang, Xiao Qi
AU - Li, Jie
AU - Liu, Jun Shan
AU - Tian, Hai Yan
PY - 2021/5/28
Y1 - 2021/5/28
N2 - 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 IC50 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.
AB - 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 IC50 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.
UR - http://www.scopus.com/inward/record.url?scp=85106529716&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.0c00840
DO - 10.1021/acs.jnatprod.0c00840
M3 - Article
C2 - 33882233
AN - SCOPUS:85106529716
SN - 0163-3864
VL - 84
SP - 1425
EP - 1433
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 5
ER -