Synthesis and Bio-evaluation of 2-Alkyl Substituted Fluorinated Genistein Analogues against Breast Cancer
Autor: | Can Xiao, Xiaohe Liu, Xu Yao, Yingli Zhu, Fan Zheng, Wenbin Zeng |
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Rok vydání: | 2022 |
Předmět: |
medicine.medical_treatment
Genistein Antineoplastic Agents Breast Neoplasms Structure-Activity Relationship chemistry.chemical_compound Breast cancer Cell Line Tumor Drug Discovery medicine Humans skin and connective tissue diseases Cell Proliferation Chemotherapy Dose-Response Relationship Drug Molecular Structure Cancer medicine.disease In vitro Molecular Docking Simulation chemistry Cell culture Cancer cell Cancer research Female Tamoxifen medicine.drug |
Zdroj: | Medicinal Chemistry. 18:589-601 |
ISSN: | 1573-4064 |
Popis: | 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. |
Databáze: | OpenAIRE |
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