Biliz Yağmur, Hasdemir Belma, Başpınar Küçük Hatice, Zaim Merve, Şentürk Ahmet Mesut, Müdüroğlu Kırmızıbekmez Aynur, Kara İhsan
Institute of Graduate Studies, Istanbul University-Cerrahpaşa, Istanbul 34320, Turkey.
Department of Chemistry, Organic Chemistry Division, Istanbul University-Cerrahpaşa, Avcilar, Istanbul 34320, Turkey.
ACS Omega. 2023 May 20;8(22):20073-20084. doi: 10.1021/acsomega.3c02361. eCollection 2023 Jun 6.
In this study, a new series of -acyl hydrazones , , and , starting from methyl δ-oxo pentanoate with different substituted groups , were synthesized as anticancer agents. The structures of obtained target molecules were identified by spectrometric analysis methods (FT-IR, H NMR, C NMR, and LC-MS). The antiproliferative activity of the novel -acyl hydrazones was evaluated on the breast (MCF-7) and prostate (PC-3) cancer cell lines by an MTT assay. Additionally, breast epithelial cells (ME-16C) were used as reference normal cells. All newly synthesized compounds , , and exhibited selective antiproliferative activity with high toxicity to both cancer cells simultaneously without any toxicity to normal cells. Among these novel -acyl hydrazones, showed the most potent anticancer activities with IC values at 7.52 ± 0.32-25.41 ± 0.82 and 10.19 ± 0.52-57.33 ± 0.92 μM against MCF-7 and PC-3 cells, respectively. Also, molecular docking studies were applied to comprehend potential molecular interactions between compounds and target proteins. It was seen that the docking calculations and the experimental data are in good agreement.
在本研究中，以具有不同取代基的δ-氧代戊酸甲酯为起始原料，合成了一系列新型的酰腙类化合物、和，作为抗癌剂。通过光谱分析方法（傅里叶变换红外光谱、核磁共振氢谱、核磁共振碳谱和液相色谱-质谱联用）对所得目标分子的结构进行了鉴定。采用MTT法评估了新型酰腙类化合物对乳腺癌（MCF-7）和前列腺癌（PC-3）细胞系的抗增殖活性。此外，乳腺上皮细胞（ME-16C）用作正常对照细胞。所有新合成的化合物、和均表现出选择性抗增殖活性，对两种癌细胞均具有高毒性，而对正常细胞无任何毒性。在这些新型酰腙类化合物中，对MCF-7和PC-3细胞的IC值分别为7.52±0.32 - 25.41±0.82和10.19±0.52 - 57.33±0.92μM，显示出最有效的抗癌活性。此外，还进行了分子对接研究，以了解化合物与靶蛋白之间潜在的分子相互作用。结果表明，对接计算结果与实验数据吻合良好。
