In vitro and in vivo studies on three new 8-hydroxyquinoline-based zinc(II) coordination compounds as potential antimelanoma cancer agents.

Herein, three new 8-hydroxyquinoline zinc(II)-based complexes (QhBr1-QhBr3) were synthesized and characterized using 8-hydroxyquinoline derivatives (H-QBr1 and H-QBr2) and o-phenanthroline-based derivatives (pyr1-pyr3). The results showed that QhBr1-QhBr3 exhibit (i) strong in vitro antitumor effects against human skin melanoma (SK-MEL-5) cells with IC50 values above 2.70-5.04 μM and (ii) excellent toxicity selectivity index (TSI) (>9.9) for IC50 (human normal liver HL-7702 or human epidermal (HaCaT cells)/IC50 (SK-MEL-5 cancer cells). Furthermore, QhBr3, featuring two ligands (QBr2 and pyr3), exhibited the strongest inhibitory effect (IE) among all 8-hydroxyquinoline zinc(II)-based coordination compounds. Notably, QhBr3 (10.0 mg/kg) exhibited an IE of 54.2 % on SK-MEL-5 tumor growth and minor in vivo side effects. Furthermore, QhBr2 and QhBr3 induced senescence and apoptosis by activating caspase, thus damaging DNA and hTERT.