Six N-phenylcarbazole/triphenylamine modified half-sandwiched iridium_((III))Schiff base compounds([(η5-Cpx)Ir(N^N)Cl]PF_(6))were synthesised and characterised in this study.The regulation and introduction of Schiff ...Six N-phenylcarbazole/triphenylamine modified half-sandwiched iridium_((III))Schiff base compounds([(η5-Cpx)Ir(N^N)Cl]PF_(6))were synthesised and characterised in this study.The regulation and introduction of Schiff bases increased the antitumor activity of these compounds(IC50:1.4±0.1μM-11.5±0.5μM).The highest antitumor activity exhibited by these compounds was nearly 13 times that of clinical cisplatin.Interestingly,these compounds could also effectively block the migration of cancer cells.These compounds were observed to bind to proteins(binding constant:~10^(4) M^(-1))and transport through serum protein,catalyse the oxidation of the coenzyme nicotinamide-adenine dinucleotide,and increase reactive oxygen species levels in cells,which resulted in an antitumor mechanism of oxidation.Laser confocal microscopy and flow cytometry studies confirmed that these compounds possessed an energydependent cellular uptake mechanism,effectively accumulated in lysosomes(Pearson co-localization coefficient:~0.75),damaged the integrity of acidic lysosomes,disrupted the cell cycle,induced a change in mitochondrial membrane potential,and eventually led to apoptosis.All these findings suggest that these compounds are potential antitumor agents with dual functions:metastasis inhibition and lysosomal damage.展开更多
Herein,a new class of iridium(Ⅲ)-based metal complexes with phosphine-imine(P^N)ligands are synthesized and authenticated.These complexes show high cytotoxicities against seven cancer cells in vitro.Simultaneously,an...Herein,a new class of iridium(Ⅲ)-based metal complexes with phosphine-imine(P^N)ligands are synthesized and authenticated.These complexes show high cytotoxicities against seven cancer cells in vitro.Simultaneously,antitumor mechanism studies show that complex Ir3 induces apoptosis by depolarization of mitochondrial membrane potential,ROS overproduction and ROS-mediated DNA damage.Importantly,BIX01294,a G9a histone methyltransferase inhibitor,could markedly sensitize Ir3-induced cytotoxicity,cell cycle arrest,apoptosis and inhibition of migration in HCT116 cancer cells in vitro.Finally,we show that combined treatment with Ir3 and BIX01294 potently inhibits tumour growth and lung metastasis in vivo.Taken together,we demonstrate that BIX01294 could potently sensitize iridium(Ⅲ)-based metal complex-induced inhibition of tumour progression and provide the basis for developing new metal-based anticancer agents and therapeutic strategies in vivo for effective cancer therapy.展开更多
Herein we present half-sandwich Ru^(II)diimine complexes that combine anticancer and antimetastasis activity into one molecule.Two half-sandwich Ru^(II)diimine complexes[(η^(6)-p-cymene)Ru(N^N)Cl]PF_(6)have been synt...Herein we present half-sandwich Ru^(II)diimine complexes that combine anticancer and antimetastasis activity into one molecule.Two half-sandwich Ru^(II)diimine complexes[(η^(6)-p-cymene)Ru(N^N)Cl]PF_(6)have been synthesized and characterized.展开更多
基金University Research Development Program of Shandong Province(J18KA082)the Student’s Platform for Innovation and Entrepreneurship Training Program(S201910446034)+1 种基金the National Natural Science Foundation of China(Grant No.21671118)the Taishan Scholars Program and the High Performance Computing Center of Qufu Normal University for their support.
文摘Six N-phenylcarbazole/triphenylamine modified half-sandwiched iridium_((III))Schiff base compounds([(η5-Cpx)Ir(N^N)Cl]PF_(6))were synthesised and characterised in this study.The regulation and introduction of Schiff bases increased the antitumor activity of these compounds(IC50:1.4±0.1μM-11.5±0.5μM).The highest antitumor activity exhibited by these compounds was nearly 13 times that of clinical cisplatin.Interestingly,these compounds could also effectively block the migration of cancer cells.These compounds were observed to bind to proteins(binding constant:~10^(4) M^(-1))and transport through serum protein,catalyse the oxidation of the coenzyme nicotinamide-adenine dinucleotide,and increase reactive oxygen species levels in cells,which resulted in an antitumor mechanism of oxidation.Laser confocal microscopy and flow cytometry studies confirmed that these compounds possessed an energydependent cellular uptake mechanism,effectively accumulated in lysosomes(Pearson co-localization coefficient:~0.75),damaged the integrity of acidic lysosomes,disrupted the cell cycle,induced a change in mitochondrial membrane potential,and eventually led to apoptosis.All these findings suggest that these compounds are potential antitumor agents with dual functions:metastasis inhibition and lysosomal damage.
基金supported by National Science Foundation of China(Grant No.21671118)the Taishan Scholars Program.
文摘Herein,a new class of iridium(Ⅲ)-based metal complexes with phosphine-imine(P^N)ligands are synthesized and authenticated.These complexes show high cytotoxicities against seven cancer cells in vitro.Simultaneously,antitumor mechanism studies show that complex Ir3 induces apoptosis by depolarization of mitochondrial membrane potential,ROS overproduction and ROS-mediated DNA damage.Importantly,BIX01294,a G9a histone methyltransferase inhibitor,could markedly sensitize Ir3-induced cytotoxicity,cell cycle arrest,apoptosis and inhibition of migration in HCT116 cancer cells in vitro.Finally,we show that combined treatment with Ir3 and BIX01294 potently inhibits tumour growth and lung metastasis in vivo.Taken together,we demonstrate that BIX01294 could potently sensitize iridium(Ⅲ)-based metal complex-induced inhibition of tumour progression and provide the basis for developing new metal-based anticancer agents and therapeutic strategies in vivo for effective cancer therapy.
基金the National Natural Science Foundation of China(Grant No.21671118)and the Taishan Scholars Program for support.
文摘Herein we present half-sandwich Ru^(II)diimine complexes that combine anticancer and antimetastasis activity into one molecule.Two half-sandwich Ru^(II)diimine complexes[(η^(6)-p-cymene)Ru(N^N)Cl]PF_(6)have been synthesized and characterized.
