Microwave-assisted synthesis of polypyridyl ruthenium(ii) complexes as potential tumor-targeting inhibitors against the migration and invasion of Hela cells through G2/M phase arrest

Abstract

A series of polypyridyl ruthenium(II) complexes coordinated by phenanthroimidazole derivatives [Ru(phen)₂(R)](ClO₄)₂ (where 1 R = IP, 2 R = PIP, 3 R = p-HPIP, 4 R = p-OCH₃PIP) was synthesized with an average yield of >85% under microwave irradiation at 140 °C for 30 min. The inhibitory effect of these complexes against various tumour cells were evaluated by MTT assay, and the results showed that these polypyridyl ruthenium(II) complexes exhibited acceptable inhibition against different tumour cells, especially 4, with an IC₅₀ of 18.4 μM for Hela cells. The results showed that 4 inhibited the growth of cervical cancer Hela cells by inducing G2/M phase arrest, which was followed by slight apoptosis. Further studies showed that 4 displayed better inhibition against the invasion and metastasis of Hela cells than NAMI-A. Studies on the in vivo distribution and metabolism indicated that 4 was rapidly distributed in the entire body, absorbed by the tumour tissue and had only a small accumulation of toxicity in the body. These results demonstrated that this type of ruthenium(II) complex can block the growth of Hela cells and inhibit their migration and invasion through G2/M phase arrest, which suggests the complex could act as a potential tumour-targeting inhibitor in future clinical applications.