Pd(II)and Rh(III)Complexes with Isoquinoline Derivatives Induced Mitochondria-Mediated Apoptotic and Autophagic Cell Death in HepG2 Cells  

作　　者：Noor Shad Gul Taj-Malook Khan Yan-Cheng Liu Muhammad Iqbal Choudhary Zhen-Feng Chen Hong Liang 

机构地区：[1]State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources,School of Chemistry and Pharmacy,Guangxi Normal University,Guilin 541004 [2]International Center for Chemical and Biological Sciences,University of Karachi,Karachi 74270

出　　处：《CCS Chemistry》2021年第6期1626-1641,共16页中国化学会会刊（英文）

基　　金：This work was supported by the National Natural Science Foundation of China(grant no.21431001);IRT_16R15,and Natural Science Foundation of Guangxi Province of China(grant nos.2016GXNSFGA380005 and AD17129007)as well as the“BAGUI Scholar”program of Guangxi Province of China.

摘　　要：Nonplatinummetal complexes of[Pd(L^(1))Cl_(2)](C1),[Rh(L^(1))Cl_(3)(DMSO)](C2),[Pd(L^(2))Cl_(2)](C3),and[Rh(L^(3))Cl_(3)(DMSO)](C4)with isoquinoline derivatives have been prepared and characterized.C1-C4 exhibited higher in vitro anticancer activity and lower toxicity than the corresponding ligands and cisplatin against HepG2 cells.The mechanistic studies revealed that C1 arrested the cell cycle at S-phase by regulation of cyclin and cyclin-dependent kinases.C1 was accumulated in mitochondria,which increased the generation of reactive oxygen species(ROS)and endoplasmic reticulum(ER)-stress response through mitochondrial dysfunction.Moreover,C1 stimulated Ca^(2+)release,activated the caspase cascade,and triggered mitochondria-mediated apoptosis.The in vivo studies of C1 demonstrated higher safety than cisplatin and effective tumor growth inhibition.C1 is a potential anticancer drug candidate.

关 键 词：palladium(II) rhodium(III) isoquinoline derivatives ANTICANCER apoptosis autophagy 

分 类 号：O6[理学—化学]