title: Targeted photocytotoxicity by copper(II) complexes having vitamin B6 and photoactive acridine moieties.
abstract: Copper(II) pyridoxal Schiff base complexes [Cu(L(1)/L(2))(B)]ClO4 (1-4), where HL(1) is 4-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (in 1 and 2), HL(2) is 2-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)phenol (in 3, 4), B is 11-(9-acridinyl)dipyrido[3,2-a:2',3'-c]phenazine (acdppz in 1 and 3), dipyrido[3,2-a:2',3'-c]phenazine (in 2) and 1,10-phenanthroline (in 4), were synthesized, characterized and their photocytotoxicity in visible light, intracellular localization, cellular uptake and DNA photocleavage activity were studied. Complex 4 was characterized by X-ray crystallography. Complexes 1 and 3 having acdppz as photosensitizer showed significant photocytotoxicity in visible light in HeLa and MCF7 cells giving IC50 value of <0.6 μM, while being relatively non-toxic in dark. The complexes were non-toxic to non-tumorigenic HPL1D cells both in light and dark conditions. Complex 1 showed significant localization in the cytoplasm of HeLa cells within 4 h of treatment, as evidenced from confocal microscopy. DCFDA assay on 1 suggested generation of intracellular reactive oxygen species in HeLa cells upon photo-exposure. Importantly, Annexin-V-FITC/PI assay indicated photo-induced apoptotic cell death.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore, 560012, India.
authors.forename: Nandini
authors.initials: N
authors.lastname: Mukherjee
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore, 560 012, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Podder
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore, 560012, India.
authors.forename: Samya
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore, 560 012, India.
authors.forename: Shamik
authors.initials: S
authors.lastname: Majumdar
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore, 560 012, India. Electronic address: nandi@biochem.iisc.ernet.in.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Nandi
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore, 560012, India. Electronic address: arc@ipc.iisc.ernet.in.
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D000166:Acridines / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003300:Copper / Q000737:chemistry*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D053837:DNA Cleavage / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D025101:Vitamin B 6 / Q000737:chemistry*
chemical_list: D000166:Acridines; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D003300:Copper; D025101:Vitamin B 6
keywords: Acridine; Copper; Medicinal chemistry; Photocytotoxicity; Tumour selectivity; Vitamin B(6)