Synthesis, structures, cellular uptake and apoptosis-inducing properties of highly cytotoxic ruthenium-Norharman complexes

Abstract

Three novel Ru(II) complexes of the general formula [Ru(N-N)(2)(Norharman)(2)](SO(3)CF(3))(2), where N-N = 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), 4,7-diphenyl-1,10-phenanthroline (DIP, 3) and Norharman (9H-pyrido[3,4-b]indole) is a naturally occurring β-carboline alkaloid, have been synthesized and characterized. The molecular structures of 1 and 2 have been determined by X-ray diffraction analysis. The cellular uptake efficiencies, in vitro cytotoxicities and apoptosis-inducing properties of these complexes have been extensively explored. Notably, 1-3 exhibit potent antiproliferative activities against a panel of human cancer cell lines with IC(50) values lower than those of cisplatin. Further studies show that 1-3 can cause cell cycle arrest in the G0/G1 phase and induce apoptosis through mitochondrial dysfunction and reactive oxygen species (ROS) generation. In vitro DNA binding studies have also been conducted to provide information about the possible mechanism of action.

Synthesis, Characterization, and Biological Evaluation of New Ru(II) Polypyridyl Photosensitizers for Photodynamic Therapy

“…Both complexes showed an overal cellular uptake 10-100 times lower than for other ruthenium complexes. 44,88,89 Remarkably, 2 and particularly 1 still exhibited moderate to high toxicity upon light irradiation. Improving the cellular uptake of these compounds (e.g.…”

“…high phototoxicity, it has to be acknowledged that their cellular uptake into HeLa cells is quite moderate compared to other Ru(II) complexes. 44,88,89 To obtain more detailed information about the localization of 1and 2their subcellular accumulation was investigated. Briefly, HeLa cells were incubated with 1 and 2 for 4 h and subsequently the nuclei and mitochondria of the cells were isolated while the remaining cell material was kept as a residual fraction.…”

Monomeric and dimeric coordinatively saturated and substitutionally inert Ru(ii) polypyridyl complexes as anticancer drug candidates

“…Among them, the apoptotic cell death through the activation of the mitochondrial dysfunctional pathway started to arise as a main cause of cytotoxicity exerted by Ru(II) polypyridyl complexes. [115][116][117][118][119] In 2010, combinatorial coordination chemistry followed by cytotoxicity screening allowed the discovery of a new antiproliferative complex ([Ru(tBu 2 bpy) 2 (phox)]PF 6 (46, Figure 10). 117 After a brief structureactivity relationship, Meggers and co-workers demonstrated that complex 46 showed the highest cytotoxicity when compared with the other tris-heteroleptic complexes tested.…”

“…Norharman is a naturally occurring β-carboline alkaloid. 119 The in vitro cytotoxicity of these complexes was evaluated against three cancer cell lines HepG2, HeLa, MCF-7 using cisplatin as a control.…”

The development and current station of marine controlled source electromagnetic transmitter in China

“…[6] Deck monitoring unitfor underwater transmitter control signal can be transmitted via the signal cable, easy to view and change the transmitter's operating status. Transmitter through a low-voltage control signal to control the high voltage inverter switches off the inverse of the DC will be added to the transmitter sent out into the desired AC waveform, the inverter AC signal waveform frequency from the deck monitoring unit issued instructions to control.…”