Department of Chemical and Materials Engineering, Southern Taiwan University of Science and Technology, Tainan City, Taiwan.
J Pharm Pharmacol. 2014 Jan;66(1):73-83. doi: 10.1111/jphp.12157. Epub 2013 Oct 25.
The aim of this research is to investigate whether the oxygen atom O(6) in the sydnone ring of 3-arylsydnone-4-carbaldehyde N(4)-phenylthiosemicarbazones (HArSYTSCs, 3a-d) is a good electron donor atom upon metal complexation. Furthermore, ligands 3a-d and the corresponding palladium complexes (Pd(ArSYTSC)Cl, 4a-d) would be expected to find their potent biological activities.
The desired palladium complexes 4a-d were first synthesized from thiosemicarbazones 3a-d. Then, the antiproliferative activity of ligands 3a-d and complexes 4a-d were tested against human hepatocellular carcinoma and human cervical epithelioid carcinoma (HeLa) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trazolium bromide (MTT) assay.
According to X-ray analyses, ligands 3a-d are bonded to the Pd (II) center in an O, N, S-tridentate coordination mode through sydnone carbonyl oxygen O(6), azomethine nitrogen and the thiolate sulfur atom. The carbonyl oxygen of the sydnone ring is found to be a good electron donor site upon metal complexation. Moreover, MTT assay results reveal that the palladium complexes 4a-d have greater antiproliferative activity than 5-fluorouracil. In particular, the complexes exhibit obvious better activity than the corresponding ligands 3a-d against HeLa cell.
The results indicate that the synthesized novel palladium complexes have greater antiproliferative activity than both 5-fluorouracil and the corresponding ligands against HeLa cell. Accordingly, the study of sydnonyl complexes bearing anticancer activities may support the development of coordination chemistry.
本研究旨在探讨 3-芳基-1,2-二氢-3-氧代-2H-1,4-苯并噻嗪-4-甲醛 N-（4-苯基硫代）缩氨硫脲（HArSYTSCs，3a-d）中 sydnone 环上的氧原子 O（6）在金属络合时是否为良好的电子供体原子。此外，配体 3a-d 和相应的钯配合物（Pd（ArSYTSC）Cl，4a-d）有望发现其有效的生物活性。
首先由缩氨硫脲 3a-d 合成所需的钯配合物 4a-d。然后，通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）测定法测试配体 3a-d 和配合物 4a-d 对人肝癌和人宫颈上皮样癌细胞（HeLa）的增殖抑制活性。
根据 X 射线分析，配体 3a-d 通过 sydnone 羰基氧 O（6）、亚胺氮和硫代硫原子与 Pd（II）中心以 O、N、S-三齿配位模式结合。发现 sydnone 环上的羰基氧在金属络合时是良好的电子供体位点。此外，MTT 测定结果表明，钯配合物 4a-d 比 5-氟尿嘧啶具有更强的增殖抑制活性。特别是，与相应的配体 3a-d 相比，这些配合物对 HeLa 细胞显示出明显更好的活性。
结果表明，与 5-氟尿嘧啶和相应的配体相比，合成的新型钯配合物对 HeLa 细胞具有更强的增殖抑制活性。因此，对具有抗癌活性的 sydnonyl 配合物的研究可能支持配位化学的发展。
