Luminescent 11-{Naphthalen-1-yl}dipyrido[3,2-a:2',3'-c]phenazine- Based Ru(II)/Ir(III)/Re(I) Complexes for HCT-116 Colorectal Cancer Stem Cell Therapy

被引:15
作者
Das, Utpal [1 ]
Shanavas, Shanooja [2 ,3 ]
Nagendra, Apoorva H. [2 ,3 ]
Kar, Binoy [1 ]
Roy, Nilmadhab [1 ]
Vardhan, Seshu [4 ]
Sahoo, Suban K. [4 ]
Panda, Debashis [5 ]
Bose, Bipasha [2 ,3 ]
Paira, Priyankar [1 ]
机构
[1] Vellore Inst Technol, Sch Adv Sci, Dept Chem, Vellore 632014, Tamilnadu, India
[2] Yenepoya Univ, Dept Stem Cells, Mangalore 575018, Karnataka, India
[3] Yenepoya Univ, Inst Yenepoya Res Ctr, Regenerat Med Ctr, Mangalore 575018, Karnataka, India
[4] S V Natl Inst Technol SVNIT Ichchanath, Dept Appl Chem, Surat 395007, Gujrat, India
[5] Rajiv Gandhi Inst Petr Technol, Inst Natl Importance GOI Act 54 2007, Dept Chem, Jais 229304, Uttar Pradesh, India
关键词
1,10-phenanthroline-5,6-dione; dichloro(p-cymene)ruthenium(II) dimer pentamethylcyclopentadienyliridium(III) chloride dimer; pentacarbonylchlororhenium(I); 11-(naphthalen-1-yl)dipyrido[3,2-a:2'3'-c]phenazine; DFT analysis; molecular docking; cell cycle analysis; CYCLOMETALATED IRIDIUM(III) COMPLEXES; METAL-COMPLEXES; DNA-BINDING; ANTICANCER; LOCALIZATION; MITOCHONDRIA; RESISTANT; TRACKING; IMPACT; PROBES;
D O I
10.1021/acsabm.2c00556
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Due to a number of unpleasant considerations, marketed drugs have steadily lost their importance in the treatment of cancer. In order to find a viable cancer cell diagnostic agent, we therefore focused on metal complexes that displayed target adequacy, permeability to cancer cells, high standard water solubility, cytoselectivity, and luminescent behavior. In this aspect, luminescent 11-{naphthalen-1-yl} dipyrido [3,2-a:2',3'-c] phenazine based Ru(II)/Ir(III)/Re(I) complexes have been prepared for HCT-116 colorectal cancer stem cell therapy. Our study successfully established the possible cytotoxicity of IrL complex at different doses on HCT-116 colorectal cancer stem cells (CRCSCs). Additionally, an immunochemistry analysis of the complex IrL showed that the molecule was subcellularly localized in the nucleus and other regions of the cytoplasm, where it caused nuclear DNA damage and mitochondrial dysfunction. The level of BAX and Bcl-2 was further quantified by qRT-PCR. The expression of proapoptotic BAX showed increased expression in the complex IrL-treated cell compared to the control, indicating the potential of complex IrL for apoptotic induction. Upon further validation, complex IrL was developed as an inhibitor of autophagy for the eradication of cancer stem cells.
引用
收藏
页码:410 / 424
页数:15
相关论文
共 58 条
[1]   Empirical Formulae to Molecular Structures of Metal Complexes by Molar Conductance [J].
Ali, Imran ;
Wani, Waseem A. ;
Saleem, Kishwar .
SYNTHESIS AND REACTIVITY IN INORGANIC METAL-ORGANIC AND NANO-METAL CHEMISTRY, 2013, 43 (09) :1162-1170
[2]   Anticancer Ruthenium(η6-p-cymene) Complexes of Nonsteroidal Anti-inflammatory Drug Derivatives [J].
Aman, Farhana ;
Hanif, Muhammad ;
Siddiqui, Waseeq Ahmad ;
Ashraf, Adnan ;
Filak, Lukas K. ;
Reynisson, Johannes ;
Soehnel, Tilo ;
Jamieson, Stephen M. F. ;
Hartinger, Christian G. .
ORGANOMETALLICS, 2014, 33 (19) :5546-5553
[3]  
[Anonymous], 2007, GLOBAL FACTS FIGURES
[4]   Luminescent anticancer Ru(II)-arenebipyridine and phenanthroline complexes: Synthesis, characterization, DFT studies, biological interactions and cellular imaging application [J].
Anuja, P. K. ;
Paira, Priyankar .
JOURNAL OF INORGANIC BIOCHEMISTRY, 2020, 208
[5]   Complexes in context: Attempting to control the cellular uptake and localisation of rhenium fac-tricarbonyl polypyridyl complexes [J].
Balasingham, Rebeca G. ;
Coogan, Michael P. ;
Thorp-Greenwood, Flora L. .
DALTON TRANSACTIONS, 2011, 40 (44) :11663-11674
[6]   Remarkable enhancement in photocytotoxicity and hydrolytic stability of curcumin on binding to an oxovanadium(IV) moiety [J].
Banerjee, Samya ;
Pant, Ila ;
Khan, Imran ;
Prasad, Puja ;
Hussain, Akhtar ;
Kondaiah, Paturu ;
Chakravarty, Akhil R. .
DALTON TRANSACTIONS, 2015, 44 (09) :4108-4122
[7]   Assessment of Oxidative Damage in the Primary Mouse Ocular Surface Cells/Stem Cells in Response to Ultraviolet-C (UV-C) Damage [J].
Bose, Bipasha ;
Kapoor, Saketh ;
Sen, Utsav ;
Nihad, Muhammad ;
Chaudhury, Debajit ;
Shenoy, Sudheer P. .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2020, (156)
[8]   Rhenium-Based Complexes and in Vivo Testing: A Brief History [J].
Capper, Miles S. ;
Packman, Hollie ;
Rehkamper, Mark .
CHEMBIOCHEM, 2020, 21 (15) :2111-2115
[9]   Anticancer activity of ruthenium(II) arene complexes bearing 1,2,3,4-tetrahydroisoquinoline amino alcohol ligands [J].
Chelopo, Madichaba P. ;
Pawar, Sachin A. ;
Sokhela, Mxolisi K. ;
Govender, Thavendran ;
Kruger, Hendrik G. ;
Maguire, Glenn E. M. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 66 :407-414
[10]   Phosphorescent iridium(III) complexes as multicolor probes for specific mitochondrial imaging and tracking [J].
Chen, Yu ;
Qiao, Liping ;
Ji, Liangnian ;
Chao, Hui .
BIOMATERIALS, 2014, 35 (01) :2-13