Synthesis and anti-breast cancer activity of novel cyclic mono-carbonyl curcumin analogues
- VernacularTitle:新型环状单羰姜黄素类似物的合成及其抗乳腺癌活性研究
- Author:
Xianhu FENG
1
;
Yongjie CHEN
1
;
Lin CHEN
1
;
Yi HOU
2
;
Wanjun CAO
1
;
Qiang SU
1
Author Information
1. Dept. of Pharmacy，Beijing Anzhen Nanchong Hospital，Capital Medical University & Nanchong Central Hospital，Sichuan Nanchong 637500，China
2. Dept. of Clinical Pharmacy，Zhongjiang County People’s Hospital，Sichuan Deyang 618100，China
- Publication Type:Journal Article
- Keywords:
curcumin;
mono-carbonyl curcumin analogues;
breast cancer;
aldol condensation reaction;
bioinformatics
- From:
China Pharmacy
2025;36(5):563-567
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To design and synthesize mono-carbonyl curcumin analogues（MCACs） and investigate the activities of them against breast cancer. METHODS The analogues F1， F2， and F3 were obtained by aldol condensation reaction， and their antitumor activities（including the activities of human breast cancer cell MCF-7 and human lung cancer cell A549） were detected by MTT assay [evaluated with half inhibitory concentration（IC50）]. The results of MTT assay were compared with those of curcumin. Bioinformatics methods were used to collect the core targets of analogues F1， F2 and F3 acting on breast cancer， and then molecular docking verification was carried out. The cell experiments were conducted to investigate the effects of high， medium and low concentrations （16， 8， 4 μmol/L） of F1， F2 and F3 on the expression of the first core target protein as well as the effects of medium concentration of F1， F2 and F3 on the expression of cleaved-caspase-3. RESULTS Compared with curcumin， IC50 of analogues F1， F2 and F3 to A549 and MCF-7 cells（except for IC50 of analogue F2 to A549 cells） were decreased significantly（P＜ 0.05 or P＜0.01）； among them， IC50 of analogue F2 to MCF-7 cell was the lowest， being（9.67±1.27） μmol/L. Bioinformatics analysis showed that index of affinity of analogues F1， F2 and F3 with the first core target epidermal growth factor receptor （EGFR）， protein kinase B （AKT） and AKT were 5.909 2， 8.402 5 and 6.486 6， respectively； high concentration of F1 could significantly reduce the phosphorylation level of EGFR protein in MCF-7 cells（P＜0.01）， while low， medium， and high concentrations of F2 and high concentration of F3 could significantly reduce the phosphorylation level of AKT protein in MCF-7 cells（P＜0.05 or P＜0.01）. Medium concentration of F1， F2， and F3 could significantly increase the expression level of cleaved- caspase-3 protein in MCF-7 cells（P＜0.01）. CONCLUSIONS Designed and synthesized MCACs F1， F2 and F3 all have good anti- breast cancer activity， and F2 has better anti-breast cancer activity.
