Strong In Vitro And Vivo Cytotoxicity Of Two Platinum(II) Complexes With Cryptolepine Derivatives

Two mononuclear Pt(II) compounds, [Pt( BQL1 )Cl]Cl ( BQL1-Pt ) and [Pt( BQL2 )Cl]Cl ( BQL2-Pt ) with [5-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-pentyl]-bis-pyridin-2-ylmethyl-amine ( BQL1 ) and [9-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-nonyl]-bis-pyridin-2-ylmethyl-amine ( BQL2 ), were prepared as new chemotypes for potential antitumor agents. This study evaluated the influence of cryptolepine derivatives in BQL1-Pt , 2,2′-dipicolylamine Pt(II) complex, and BQL2-Pt on cellular Pt(II) accumulation, cytotoxicity, and in vitro and in vivo antitumor activities against T-24 cancer cells and normal HL-7702 cells. BQL1-Pt and BQL2-Pt displayed cytotoxic activities in the micromole range (1.3±0.1 and 0.2±0.2 μM, respectively) on T-24 cancer cells; however, they did not exhibit any toxicity against HL-7702 cells. They triggered T-24 cell apoptosis through a mitochondrial dysfunction pathway. Compared to 2,2′-dipicolylamine, the neutral BQL1 and BQL2 ligands with cryptolepine derivatives increased the planarity and branched chain resulting in BQL1-Pt and BQL2-Pt with favorable antitumor activities. Further, BQL2-Pt effectively inhibited the growth of bladder T-24 tumor in vivo . BQL2-Pt can act as a potential therapeutic candidate for cancer treatment.