Synthesis of bufalin derivatives with inhibitory activity against prostate cancer cells.
Bufalin possesses a strong anti-cancer effect, but the cardiac toxicity targeting the Na(+), K(+)-ATPase limits its application. Here, two bufalin derivatives, bufadienolactam (1) and secobufalinamide (2), were synthesised by treating bufalin with ammonium acetate in dimethylformamide solution. Their structures were elucidated by extensive spectroscopic methods. The structure of compound 2 was further confirmed by single-crystal X-ray diffraction analysis. Compounds 1 and 2 expressed strong inhibitory activities against androgen-dependent prostate cancer cells (IC₅₀ values about 10 μM), but only weak inhibition on Na(+), K(+)-ATPase (Ki about 70 μM), indicating that they might be potential anti-prostate cancer agents without severe cardiac toxicity.
a Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research , College of Pharmacy, Jinan University , Guangzhou 510632 , P.R. China.
Xiao-Feng
XF
Yuan
Hai-Yan
HY
Tian
Juan
J
Li
Lu
L
Jin
Shu-Tai
ST
Jiang
Ken Wing-Keung
KW
Liu
Cheng
C
Luo
David A
DA
Middleton
Mikael
M
Esmann
Wen-Cai
WC
Ye
Ren-Wang
RW
Jiang
D000970:Antineoplastic Agents / Q000494:pharmacology; D002018:Bufanolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D002018:Bufanolides; D004791:Enzyme Inhibitors; C000592198:bufadienolactam; C000592199:secobufalinamide; D000254:Sodium-Potassium-Exchanging ATPase; C022777:bufalin
K+-ATPase; Na+; androgen receptor; bufalin; prostate cancer