478919-25-4Relevant academic research and scientific papers
Synthesis and evaluation of electron-rich curcumin analogues
Amolins, Michael W.,Peterson, Laura B.,Blagg, Brian S.J.
experimental part, p. 360 - 367 (2011/02/26)
The natural product curcumin has long been recognized for its medicinal properties and is utilized for the treatment of many diseases. However, it remains unknown whether this activity is based on its presumably promiscuous scaffold, or if it results from the Michael acceptor properties of the α,β-unsaturated 1,3-diketone moiety central to its structure. To probe this issue, electron-rich pyrazole and isoxazole analogues were prepared and evaluated against two breast cancer cell lines, which resulted in the identification of several compounds that exhibit low micromolar to mid nanomolar anti-proliferative activity. A conjugate addition study was also performed to compare the relative electrophilicity of the diketone, pyrazole and isoxazole analogues.
Antitumor agents. 217. Curcumin analogues as novel androgen receptor antagonists with potential as anti-prostate cancer agents
Ohtsu, Hironori,Xiao, Zhiyan,Ishida, Junko,Nagai, Masahiro,Wang, Hui-Kang,Itokawa, Hideji,Su, Ching-Yuan,Shih, Charles,Chiang, Tzuying,Chang, Eugene,Lee, YiFen,Tsai, Meng-Yin,Chang, Chawnshang,Lee, Kuo-Hsiung
, p. 5037 - 5042 (2007/10/03)
A number of curcumin analogues were prepared and evaluated as potential androgen receptor antagonists against two human prostate cancer cell lines, PC-3 and DU-145, in the presence of androgen receptor (AR) and androgen receptor coactivator, ARA70. Compounds 4 [5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one], 20 [5-hydroxy-1,7-bis[3-methoxy-4-(methoxycarbonylmethoxy)phenyl]-1, 4,6-heptatrien-3-one], 22 [7-(4-hydroxy-3-methoxyphenyl)-4-[3(4-hydroxy-3-methoxyphenyl) acryloyl]-5-oxohepta-4,6-dienoic acid ethyl ester], 23 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl] 5-oxohepta-4,6-dienoic acid], and 39 [bis(3,4-dimethoxyphenyl)-1,3-propanedione] showed potent antiandrogenic activities and were superior to hydroxyflutamide, which is the currently available antiandrogen for the treatment of prostate cancer. Structure-activity relationship (SAR) studies indicated that the bis(3,4-dimethoxyphenyl) moieties, the conjugated β-diketone moiety, and the intramolecular symmetry of the molecules seem to be important factors related to antiandrogenic activity. The data further suggest that the coplanarity of the β-diketone moiety and the presence of a strong hydrogen bond donor group were also crucial for the antiandrogenic activity, which is consistent with previous SAR results for hydroxyflutamide analogues. When the pharmacophoric elements of dihydrotestosterone (DHT) and compound 4 are superposed, the resulting construct implies that the curcumin analogues may function as a 17α-substituted DHT. Compounds 4, 20, 22, 23, and 39 have been identified as a new class of antiandrogen agents, and these compounds or their new synthetic analogues could be developed into clinical trial candidates to control androgen receptor-mediated prostate cancer growth.
