Laboratory of Organometallic Chemistry, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Avda. Libertador Bernardo O'Higgins 3363, Estación Central, Santiago, Chile.
Dalton Trans. 2018 Jan 23;47(4):1233-1242. doi: 10.1039/c7dt04344a.
Substituted amino-piperazine derivatives were synthesized and used as precursors for the preparation of a series of new organometallic Re(i) imine complexes with the general formula [(η-CHCH[double bond, length as m-dash]N-(CH)-Pz-R)Re(CO)] (Pz-R: -alkyl or aryl piperazine). The piperazine-based ligands were designed to be potential inhibitors of GSK-3β kinase. All the ligands and complexes were fully characterized and evaluated against the HT-29 and PT-45 cancer cell lines, in which GSK-3β plays a crucial role. In this context, we carried out biological evaluation using the MTT colorimetric assay. In terms of structure activity relationship, our findings indicated improved biological activity when aromaticity increased in the organic ligands (3d). In addition, the presence of the rhenium fragment in the imines (5a-d) leads to better activity with IC values in the range of 25-100 μM. In addition, our experimental studies were complemented by computational studies, where the volume and electrostatic surface of the organic ligands and organometallic compounds as well as their binding to the kinase protein are calculated.
取代的氨基哌嗪衍生物被合成，并用作一系列新的有机金属 Re(i)亚胺配合物的前体，其通式为[(η-CHCH[双键，长度为破折号]N-(CH)-Pz-R)Re(CO)]（Pz-R：-烷基或芳基哌嗪）。基于哌嗪的配体被设计为 GSK-3β激酶的潜在抑制剂。所有的配体和配合物都经过了充分的表征，并针对 HT-29 和 PT-45 癌细胞系进行了评估，在这些细胞系中，GSK-3β 起着至关重要的作用。在这方面，我们使用 MTT 比色法进行了生物评价。就构效关系而言，我们的研究结果表明，当有机配体中的芳香性增加时，生物活性得到了提高（3d）。此外，亚胺（5a-d）中铼片段的存在导致活性更好，IC 值在 25-100 μM 范围内。此外，我们的实验研究还辅以计算研究，计算了有机配体和有机金属化合物的体积和静电表面及其与激酶蛋白的结合。
