Department of Chemistry and Chemical Processing Technologies, Vocational School of Technical Sciences, Batman University, Batman, Turkey.
Medical Services and Techniques Department, Vocational School of Health Services, Gaziantep University, Gaziantep, Turkey.
Bioorg Chem. 2022 Dec;129:106176. doi: 10.1016/j.bioorg.2022.106176. Epub 2022 Oct 4.
In this study, two chiral Schiff base ligands (L1 and L2) were synthesized from the condensation reaction of (S)-2-amino-3-phenyl-1-propanol with 2-hydroxybenzaldehyde and 2-hydroxy-1-naphthaldehyde as metal precursors for the preparation of transition metal complexes with Pd(II), Fe(II), Ni(II) and Cu(II). The compounds were characterized by using X-ray (for L1-Pd(II)), NMR, FT-IR, UV-Vis, magnetic susceptibility, molar conductivity, and elemental analysis. The in vitro cytotoxic effects of ligands (L1 and L2) and their metal complexes on colon cancer cells (DLD-1), breast cancer cells (MDA-MB-231) and healthy lung human cell lines were investigated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyl tetrazolium bromide (MTT) assay. Among the synthesized compounds, L1-Pd(II) was particularly found to be the most potent anticancer drug candidate in this series with IC values of 4.07, and 9.97 µM in DLD-1 and MDA-MB-231 cell lines, respectively. In addition, molecular docking results indicate that Glu122, Asn103, Ala104, Lys126, Phe114, Leu123, and Lys126 amino acids are the binding site of the colon cancer antigen protein, in which the most active complex, L1-Pd(II) can inhibit the current target.
在这项研究中，从（S）-2-氨基-3-苯基-1-丙醇与 2-羟基苯甲醛和 2-羟基-1-萘甲醛的缩合反应中合成了两种手性希夫碱配体（L1 和 L2），作为金属前体用于制备过渡金属配合物与 Pd（II），Fe（II），Ni（II）和 Cu（II）。通过 X 射线（用于 L1-Pd（II）），NMR，FT-IR，UV-Vis，磁化率，摩尔电导率和元素分析对化合物进行了表征。通过使用 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴盐（MTT）测定法研究了配体（L1 和 L2）及其金属配合物对结肠癌细胞（DLD-1），乳腺癌细胞（MDA-MB-231）和健康肺人细胞系的体外细胞毒性作用。在所合成的化合物中，L1-Pd（II）被发现是该系列中最有效的抗癌药物候选物，其在 DLD-1 和 MDA-MB-231 细胞系中的 IC 值分别为 4.07 和 9.97 µM。此外，分子对接结果表明，Glu122，Asn103，Ala104，Lys126，Phe114，Leu123 和 Lys126 氨基酸是结肠癌抗原蛋白的结合位点，其中最活跃的复合物 L1-Pd（II）可以抑制当前的靶标。
