Abstract：
Eight Novel chalcones were synthesized and their structures were confirmed by different spectral tools. All the prepared compounds were subjected to SRB cytotoxic screening against several cancer cell lines. Compound 5c exerted the most promising effect against MCF7 and HEP2 cells with IC50 values of 9.5 and 12 µg/mL, respectively. Real-time PCR demonstrated the inhibitory effect of compound 5c on the expression level of Antigen kiel 67 (KI-67), Survivin, Interleukin-1beta (IL-1B), Interleukin-6 (IL-6), Cyclooxygenase-2 (COX-2) and Protein kinase B (AKT1) genes. Flow-cytometric analysis of the cell cycle indicated that compound 5c stopped the cell cycle at the G0/G1 and G2/M phases in MCF7 and HEP2 treated cells, respectively. ELISA assay showed that Caspase 8, Caspase 9, P53, BAX, and Glutathione (GSH) were extremely activated and Matrix metalloproteinase 2 (MMP2), Matrix metalloproteinase 9 (MMP9), BCL2, Malondialdehyde (MDA), and IL-6 were deactivated in 5c treated MCF7 and HEP2 cells. Wound healing revealed that chalcone 5c reduced the ability to close the scrape wound and decreased the number of migrating MCF7 and HEP2 cells compared to the untreated cells after 48 h. Theoretical molecular modeling against P53 cancer mutant Y220C and Bcl2 showed binding energies of -22.8 and -24.2 Kcal/mole, respectively, which confirmed our ELISA results.
摘要：
合成了八种新型查耳酮，并通过不同的光谱工具证实了它们的结构。对所有制备的化合物进行针对几种癌细胞系的SRB细胞毒性筛选。化合物5c对MCF7和HEP2细胞发挥了最有希望的作用，IC50值为9.5和12μg/mL，分别。实时PCR证明了化合物5c对抗原kiel67(KI-67)表达水平的抑制作用,幸存者,白细胞介素-1β（IL-1B），白细胞介素-6(IL-6),环氧合酶-2(COX-2)和蛋白激酶B(AKT1)基因。细胞周期的流式细胞术分析表明，化合物5c在MCF7和HEP2处理的细胞中，在G0/G1和G2/M阶段停止细胞周期。分别。ELISA检测结果显示,Caspase8、Caspase9、P53、BAX、谷胱甘肽（GSH）被极度激活，基质金属蛋白酶2（MMP2），基质金属蛋白酶9(MMP9),BCL2，丙二醛（MDA），在5c处理的MCF7和HEP2细胞中,IL-6失活。伤口愈合表明，与48小时后未处理的细胞相比，查尔酮5c降低了闭合刮擦伤口的能力，并减少了迁移的MCF7和HEP2细胞的数量。针对P53癌症突变体Y220C和Bcl2的理论分子模型显示，结合能为-22.8和-24.2Kcal/mole，分别,这证实了我们的ELISA结果。
