Bezmialem Vakif University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Fatih, 34093, Istanbul, Türkiye.
Bezmialem Vakif University, Faculty of Pharmacy, Department of Biochemistry, Fatih, 34093, Istanbul, Türkiye.
Chem Biodivers. 2023 Aug;20(8):e202300773. doi: 10.1002/cbdv.202300773. Epub 2023 Jul 17.
In this study, twenty new anthranilic acid hydrazones 6-9 (a-e) were synthesized and their structures were characterized by Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance ( H-NMR - C-NMR), and High-resolution Mass Spectroscopy (HR-MS). The inhibitory effects of the compounds against COX-II were evaluated. IC values of the compounds were found in the range of >200-0.32 μM and compounds 6e, 8d, 8e, 9b, 9c, and 9e were determined to be the most effective inhibitors. Cytotoxic effects of the most potent compounds were investigated against human hepatoblastoma (Hep-G2) and human healthy embryonic kidney (Hek-293) cell lines. Doxorubicin (IC : 8.68±0.16 μM for Hep-G2, 55.29±0.56 μM for Hek-293) was used as standard. 8e is the most active compound, with low IC against Hep-G2 (4.80±0.04 μM), high against Hek-293 (159.30±3.12), and high selectivity (33.15). Finally, molecular docking and dynamics studies were performed to understand ligand-protein interactions between the most potent compounds and COX II, Epidermal Growth Factor Receptor (EGFR), and Transforming Growth Factor beta II (TGF-βII). The docking scores were calculated in the range of -10.609--6.705 kcal/mol for COX-II, -8.652--7.743 kcal/mol for EGFR, and -10.708--8.596 kcal/mol for TGF-βII.
在这项研究中，合成了二十种新的邻氨基苯甲酰腙 6-9（a-e），并通过傅里叶变换红外（FT-IR）、核磁共振（H-NMR - C-NMR）和高分辨率质谱（HR-MS）对其结构进行了表征。评估了化合物对 COX-II 的抑制作用。发现化合物的 IC 值在>200-0.32 μM 范围内，化合物 6e、8d、8e、9b、9c 和 9e 被确定为最有效的抑制剂。对最有效的化合物进行了针对人肝癌（Hep-G2）和人正常胚胎肾（Hek-293）细胞系的细胞毒性作用研究。阿霉素（IC：Hep-G2 为 8.68±0.16 μM，Hek-293 为 55.29±0.56 μM）用作标准。8e 是最活跃的化合物，对 Hep-G2 的 IC 低（4.80±0.04 μM），对 Hek-293 的 IC 高（159.30±3.12），选择性高（33.15）。最后，进行了分子对接和动力学研究，以了解最有效化合物与 COX-II、表皮生长因子受体（EGFR）和转化生长因子β II（TGF-βII）之间的配体-蛋白相互作用。对接分数的计算范围为 COX-II 为-10.609--6.705 kcal/mol，EGFR 为-8.652--7.743 kcal/mol，TGF-βII 为-10.708--8.596 kcal/mol。
