BACKGROUND Curcuminoids, flavoring, and coloring agents in food have potent antioxidant, anti-tumor activity, and anti-inflammatory effects. However, they are rapidly metabolized to lesser active metabolites. Therefore, various studies have been conducted to synthesize new and stable curcumin analogues with enhanced therapeutic activity. METHODS Fluorinated curcumin compounds (2a-2f) were synthesized by Knoevenagel condensation between fluorobenzaldehydes (1a-1f) with curcumin. Fluorinated demethoxycurcumin (3a) was synthesized by condensation between demethoxycurcumin and 3,4-difluorobenzaldehyde (1f). The structures of these compounds were confirmed by FTIR, 1H-NMR, 13C-NMR, 19FNMR, and mass spectroscopy. Antiproliferative activities of these synthetic compounds were evaluated against breast cancer cells (4T1), melanoma cancer cells (B16F10), and normal cell lines (NIH 3T3) using MTT assay. The interaction of curcumin, 2f and 3a with several proteins (1HCL, 2ZOQ, 3D94, 5EW3, 4WA9, 1XKK, 6CCY) was investigated. The structural preservation of the epidermal growth factor receptor (EGFR) was investigated by molecular dynamics simulation. RESULTS The spectroscopic data obtained confirmed the proposed structure of fluorinated analogues. The results showed that compounds 2f and 3a inhibited cancer cells proliferation significantly more than other compounds. Compounds 2f and 3a showed the highest affinity and lowest binding energy with EGFR. The binding energies were -7.8, -10, and - 9.8 kcal/mol for curcumin, 2f and 3a with EGFR, respectively. The molecular docking results demonstrated that compounds 2f and 3a were firmly bound in a complex with EGFR via the formation of a hydrogen bond. CONCLUSION In summary, we found that fluorinated demethoxycurcumin and fluorinated curcumin induces cancer cell death and binds to EGFR with high affinity.

中文翻译：

---

氟化姜黄素类似物的抗增殖潜力：实验和计算分析与文献回顾。

背景技术食品中的姜黄素、调味剂和着色剂具有有效的抗氧化、抗肿瘤活性和抗炎作用。然而，它们会迅速代谢成活性较低的代谢物。因此，已经进行了各种研究以合成具有增强治疗活性的新的稳定的姜黄素类似物。方法通过氟苯甲醛(1a-1f)与姜黄素的Knoevenagel缩合合成含氟姜黄素化合物(2a-2f)。通过脱甲氧基姜黄素与 3,4-二氟苯甲醛 (1f) 的缩合合成氟化脱甲氧基姜黄素 (3a)。这些化合物的结构通过FTIR、1H-NMR、13C-NMR、19FNMR和质谱确认。评估了这些合成化合物对乳腺癌细胞 (4T1)、黑色素瘤癌细胞 (B16F10)、和正常细胞系 (NIH 3T3) 使用 MTT 测定。研究了姜黄素、2f 和 3a 与几种蛋白质（1HCL、2ZOQ、3D94、5EW3、4WA9、1XKK、6CCY）的相互作用。通过分子动力学模拟研究表皮生长因子受体（EGFR）的结构保存。结果获得的光谱数据证实了氟化类似物的拟议结构。结果表明，化合物2f和3a对癌细胞增殖的抑制作用明显优于其他化合物。化合物2f和3a与EGFR的亲和力最高，结合能最低。姜黄素、2f 和 3a 与 EGFR 的结合能分别为 -7.8、-10 和 -9.8 kcal/mol。分子对接结果表明化合物2f和3a与EGFR通过氢键的形成牢固地结合成复合物。