Affiliation:
1. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
2. Group of Lead Compound,
Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang, China
Abstract
Background:
Breast cancer is the leading cause of cancer death in women. The current
methods of chemotherapy for breast cancer generally have strong adverse reactions and drug resistance.
Therefore, the discovery of novel anti-breast cancer lead compounds is urgently needed.
Objective:
This study aimed to design and synthesize a series of 2-alkyl substituted fluorinated
genistein analogues and evaluate their anti-breast cancer activity.
Methods:
Target compounds were obtained in a multistep reaction synthesis. The anti-tumor activity
of compounds I-1~I-35 was evaluated with MCF-7, MDA-MB-231, MDA-MB-435, and MCF-10A
cell lines in vitro, with tamoxifen as the positive control. Molecular docking was used to study the
interaction between the synthesized compounds and PI3K-gamma.
Results:
A series of 2-alkyl substituted fluorinated genistein analogues was designed, synthesized,
and screened for their bioactivity. Most of the compounds displayed better selectivity toward breast
cancer cell lines as compared to tamoxifen. Among these analogues, I-2, I-3, I-4, I-9, I-15, and I-17
have the strongest selective inhibition of breast cancer cells. Compounds I-10, I-13, I-15, I-17, and I-
33 were found to have significant inhibitory effects on breast cancer cells. Molecular docking studies
have shown that these compounds may act as PI3Kγ inhibitors and may further exhibit anti-breast
cancer effects.
Conclusion:
Most of the newly synthesized compounds could highly, selectively inhibit breast cancer
cell lines. The experimental results indicate that the synthesized analogs may also have obvious
selective inhibitory effects on other malignant proliferation cancer cells.
Publisher
Bentham Science Publishers Ltd.
Cited by
1 articles.
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