Mitochondrial selectivity and remarkable photocytotoxicity of a ferrocenyl neodymium(iii) complex of terpyridine and curcumin in cancer cells12. Issue 15 (7th March 2016)

• Record Type: Journal Article
• Authors: Sarkar, Tukki; Banerjee, Samya; Mukherjee, Sanjoy; Hussain, Akhtar
• Is Part Of: Dalton transactions. Volume 45:Issue 15(2016)
• Page Start: 6424
• Page End: 6438
• Publication Date: 2016-03-07
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c5dt04775g
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : A mixed-ligand neodymium(iii ) complex of ferrocene appended terpyridine and curcumin targets the mitochondria and shows remarkable visible-light induced cytotoxicity in HeLa and MCF-7 cancer cells while being much less toxic in dark and to MCF-10A normal cells. Abstract : A series of four novel neodymium(iii ) complexes of the formulation [Nd(R-tpy)( O – O )(NO3 )2 ] (1–4 ), where R-tpy is 4′-phenyl-2, 2′:6′, 2′′-terpyridine (Ph-tpy;1, 2 ) and 4′-ferrocenyl-2, 2′:6′, 2′′-terpyridine (Fc-tpy;3, 4 ); O – O is the conjugate base of acetylacetone (Hacac;1, 3 ) or curcumin (Hcurc;2, 4 ), are synthesized and characterized. The single crystal structure of1 shows that the complex is a discrete mononuclear species with the Nd(iii ) centre in a nine coordinate environment provided by a set of O6 N3 donor atoms. Complexes1 and3 having the simple acac ligand are prepared as control compounds. Complex4, possessing an appended ferrocenyl (Fc) and the curcumin moiety, is remarkably photocytotoxic to HeLa and MCF-7 cancer cells in visible light giving respective IC50 values of 0.7 μM and 2.1 μM while being significantly less toxic to MCF-10A normal cells (IC50 = 34 μM) and in the dark (IC50 > 50 μM). The phenyl appended complex2, lacking a ferrocenyl moiety, is significantly less toxic to both the cell lines when compared with4 . Complexes1 and3, lacking the photoactive curcumin moiety, do not show any apparent toxicity both in light and in the dark. The cell death is apoptotic in nature and is mediated by the light-induced formation of reactive oxygen species (ROS). Fluorescence imaging experiment with HeLa cells reveals mitochondrial accumulation of complex4 within 4 h of incubation. The complexes bind to calf thymus (ct) DNA with moderate affinity giving K b values in the range of 10 4 –10 5 M −1 . The curcumin complexes2 and4 cleave plasmid supercoiled DNA to its nicked circular form in visible light via 1 O2 and ˙OH pathways. The presence of the ferrocenyl moiety is likely to be responsible for the enhanced cellular uptake and photocytotoxicity of complex4 . Thus, the mitochondria targeting complex4, being remarkably cytotoxic in light but non-toxic in the dark and to normal cells, is a potential candidate for photochemotherapeutic applications.