Synthesis and evaluation of curcumin analogues as potential thioredoxin reductase inhibitors.
Series of curcumin derivatives were synthesized; the inhibitory activities on thioredoxin reductase (TrxR) of all analogues were evaluated by DTNB assay in vitro. It is found that most of the analogues can inhibit TrxR in the low micromolar range; Structure-activity relationship analysis reveals that analogues with furan moiety have excellent inhibitory effect on TrxR in an irreversible manner, indicating that the furan moiety may serve as a possible pharmacophore during the interaction of curcumin analogues with TrxR. The effect of selected curcuminoids on growth of different TrxR overexpressed cancer cell lines was also investigated and discussed.
Qiu
Xu
X
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, China.
Liu
Zhong
Z
Shao
Wei-Yan
WY
Liu
Xing
X
Jing
Da-Ping
DP
Yu
Yan-Jun
YJ
An
Lin-Kun
LK
Huang
Shi-Liang
SL
Bu
Xian-Zhang
XZ
Huang
Zhi-Shu
ZS
Gu
Lian-Quan
LQ
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005663:Furans; D013880:Thioredoxin-Disulfide Reductase; D003474:Curcumin