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Threewater-soluble ruthenium(II) complexes with chiral 4-(2,3-dihydroxypropyl)-formamideoxoaporphine (FOA) were synthesized and characterized. It was foundthat these ruthenium(II) complexes exhibited considerable in vitroanticancer activities and that they were the effective stabilizersof telomeric and G-quadruplex-DNA (G4-DNA) in promoter of c-myc, whichacted as a telomerase inhibitor targeting G4-DNA and induced cellsenescence and apoptosis. Interestingly, the in vitro anticancer activityof 6(LC-003) was higher than those of 4(LC-001) and 5(LC-002), more selective for BEL-7404cells than for normal HL-7702 cells, and preferred to activate caspases-3/9.The different biological behaviors of the ruthenium complexes couldbe correlated with the chiral nature of 4-(2,3-dihydroxypropyl)-formamideoxoaporphine. More significantly, 6exhibited effectiveinhibitory on tumor growth in BEL-7402 xenograft mouse model and higherin vivo safety than cisplatin. These mechanistic insights indicatethat 6displays low toxicity and can be a novel anticancerdrug candidate. [ABSTRACT FROM AUTHOR]

Two G-quadruplex ligands [Pt(La)(DMSO)Cl] (Pt1) and [Pt(Lb)(DMSO)Cl] (Pt2) have been synthesized and fully characterized. The two complexes are more selective for SK-OV-3/DDP tumor cells versus normal cells (HL-7702). It was found that both Pt1 and Pt2 could be a telomerase inhibitor targeting G-quadruplex DNA. This is the first report demonstrating that telomeric, c-myc, and bcl-2 G-quadruplexes and caspase-3/9 preferred to bind with Pt2 rather than Pt1, which also can induce senescence and apoptosis. The different biological behavior of Pt1 and Pt2 may correlate with the presence of a 6-hydroxyl group in Lb. Importantly, Pt1 and Pt2 exhibited higher safety in vivo and more effective inhibitory effects on tumor growth in the HCT-8 and NCI-H460 xenograft mouse model, compared with cisplatin. Taken together, these mechanistic insights indicate that both Pt1 and Pt2 display low toxicity and could be novel anticancer drug candidates. [ABSTRACT FROM AUTHOR]