Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
Institute of Optical Materials and Technologies "Acad. Jordan Malinovski", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Molecules. 2022 Aug 26;27(17):5493. doi: 10.3390/molecules27175493.
Gallium (III) complexes with the ligands 5-bromosalicylaldehyde-4-hydroxybenzoylhydrazone and 5-bromosalicylaldehyde isonicotinoylhydrazone were synthesized to receive compounds with improved antiproliferative action. Compounds were characterized by elemental analysis, IR, and NMR spectroscopy. Density functional theory calculations with Becke's 3-parameter hybrid functional and 6-31+G(d,p) basis set were carried out to investigate the structural features of the ligands and Ga(III) complexes. Cytotoxic screening by MTT-dye reduction assay was carried out using cisplatin and melphalan as reference cytotoxic agents. A general formula [Ga(HL)]NO for the complexes obtained was suggested. The complexes are mononuclear with the Ga(III) ions being surrounded by two ligands. The ligands acted as monoanionic tridentate (ONO) donor molecules. The analysis revealed coordination binding through deprotonated phenolic-oxygen, azomethine-nitrogen, and amide-oxygen atoms. The bioassay demonstrated that all compounds exhibited concentration-dependent antiproliferative activity at low micromolar concentrations against the acute myeloid leukemia HL-60 and T-cell leukemia SKW-3 cell lines. IC values of 5-bromo-derivative ligands and gallium (III) complexes are lower than those of cisplatin and much lower than these of melphalan. The coordination to gallium (III) additionally increased the cytotoxicity compared to the metal-free hydrazones.
合成了具有 5-溴水杨醛-4-羟基苯甲酰腙和 5-溴水杨醛异烟酰腙配体的镓（III）配合物，以获得具有改善的抗增殖作用的化合物。通过元素分析、IR 和 NMR 光谱对化合物进行了表征。使用 Becke 的 3-参数混合泛函和 6-31+G(d,p)基组进行密度泛函理论计算，以研究配体和 Ga(III)配合物的结构特征。通过 MTT 染料还原测定法进行细胞毒性筛选，使用顺铂和苯丙氨酸作为参考细胞毒性剂。建议获得的配合物的通式为[Ga(HL)]NO。配合物为单核，Ga(III)离子被两个配体包围。配体充当单价三齿（ONO）供体分子。分析表明，通过酚氧、亚氨基氮和酰胺氧原子的去质子化发生配位键合。生物测定表明，所有化合物在低微摩尔浓度下对急性髓性白血病 HL-60 和 T 细胞白血病 SKW-3 细胞系均表现出浓度依赖性的抗增殖活性。5-溴衍生物配体和镓（III）配合物的 IC 值低于顺铂，远低于苯丙氨酸。与金属自由腙相比，与镓（III）配位还增加了细胞毒性。
