Application of cyclometalated rhodium(III) complexes as therapeutic agents in biomedical and luminescent cellular imaging

The synthesis and characterization of three [Rh(ppy)2(N^N)][PF6] complexes, [Rh(ppy)2(pybtz)][PF6].CH3OH (Rh1), [Rh(ppy)2(pzbtz)][PF6] (Rh2) and [Rh(ppy)2(qbtz)][PF6] (Rh3) [Hppy: 2-phenylpyridine; N^N: (pyridin-2-yl)benzo[d]thiazole (pybtz), (pyrazin-2-yl)benzo[d]thiazole (pzbtz), and (quinolin-2-yl)benzo[d]thiazole (qbtz)], and single crystal structures of Rh1 and Rh3 are reported. Rh1 and Rh3 show high fluorescent intensities upon excitation at 400 and 410 nm, respectively. Evaluation of lipophilicity by theoretical calculations indicates Rh3 > Rh1 > Rh2, introducing Rh3 as the best candidate for biological studies. The Rh3 exhibits anticancer activity, with high cellular uptake efficiency and good cytotoxicity against MCF-7 cell line as compared to the non-malignant MRC-5 cells. Flow cytometry have confirmed the apoptosis cell death and cell cycle arrest in the sub-G1 phase. The result of real time PCR shows that Rh3 induces apoptosis by up-regulating of p53, miR-15a, miR-16–1 and miR-29b and down regulating of bcl-2 and miR-21 at the level of RNA transcription. Importantly, cell imaging experiments have demonstrated that Rh3 can be considered as a new promising metallodrug candidate for cancer treatment