New organometallic imines of rhenium(i) as potential ligands of GSK-3β: synthesis, characterization and biological studiesElectronic supplementary information (ESI) available: Characterization of new arylpiperazine ligands and rhenium derivatives; cytotoxicity studies. See 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 5 -C 5 H 4 CH&z.dbd;N-(CH 2 ) 5 -Pz-R)Re(CO) 3 ] (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 50 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. Amino-piperazines and organometallic imines were synthetized and evaluated in HT-29 and PT-45 cancer cell lines. Computational studies were also developed.