TY - JOUR
T1 - Novel tetranuclear PdII and PtII anticancer complexes derived from pyrene thiosemicarbazones
AU - Oliveira, Carolina G.
AU - Romero-Canelón, Isolda
AU - Coverdale, James P. C.
AU - Maia, Pedro Ivo S.
AU - Clarkson, Guy J.
AU - Deflon, Victor M.
AU - Sadler, Peter J.
PY - 2020/6/30
Y1 - 2020/6/30
N2 - Cyclometallated palladium(II) and platinum(II) pyrenyl-derived thiosemicarbazone (H2PrR) complexes of the type [M4(μ-S-PrR-κ3-C,N,S)4] (M = PdII, PtII; R = ethyl, cyclohexyl) have been synthesised in good yields and fully characterised. X-ray crystallography showed that the tetranuclear complex [Pt4(μ-S-PrCh-κ3-C,N,S)4](CH3)2COCHCl3 contains an eight-membered ring of alternating M–S atoms. The ethyl derivatives [M4(μ-S-PrEt-κ3-C,N,S)4] exhibit potent antiproliferative activity towards A2780 human ovarian cancer cells, with IC50 values of 1.27 μM (for M = PdII) and 0.37 μM (for M = PtII), the latter being an order of magnitude more potent than the anticancer drug cisplatin (IC50 1.20 μM). These promising complexes had low toxicity towards non-cancerous human MRC5 cells, which points towards an early indication of differential toxicity between cancer and normal cells. Experiments that investigated the effects of these tetranuclear complexes on the cell cycle, integrity of the cell membrane, and induction of apoptosis, suggested that their mechanism of action of does not involve DNA targeting, unlike cisplatin, and therefore could be promising for combatting cisplatin resistance.
AB - Cyclometallated palladium(II) and platinum(II) pyrenyl-derived thiosemicarbazone (H2PrR) complexes of the type [M4(μ-S-PrR-κ3-C,N,S)4] (M = PdII, PtII; R = ethyl, cyclohexyl) have been synthesised in good yields and fully characterised. X-ray crystallography showed that the tetranuclear complex [Pt4(μ-S-PrCh-κ3-C,N,S)4](CH3)2COCHCl3 contains an eight-membered ring of alternating M–S atoms. The ethyl derivatives [M4(μ-S-PrEt-κ3-C,N,S)4] exhibit potent antiproliferative activity towards A2780 human ovarian cancer cells, with IC50 values of 1.27 μM (for M = PdII) and 0.37 μM (for M = PtII), the latter being an order of magnitude more potent than the anticancer drug cisplatin (IC50 1.20 μM). These promising complexes had low toxicity towards non-cancerous human MRC5 cells, which points towards an early indication of differential toxicity between cancer and normal cells. Experiments that investigated the effects of these tetranuclear complexes on the cell cycle, integrity of the cell membrane, and induction of apoptosis, suggested that their mechanism of action of does not involve DNA targeting, unlike cisplatin, and therefore could be promising for combatting cisplatin resistance.
UR - https://doi.org/10.1039/D0DT01133A
U2 - 10.1039/D0DT01133A
DO - 10.1039/D0DT01133A
M3 - Article
SN - 1477-9234
SP - 9595
EP - 9604
JO - Dalton Transactions
JF - Dalton Transactions
IS - 28
ER -
