title: Endoplasmic reticulum targeting tumour selective photocytotoxic oxovanadium(IV) complexes having vitamin-B6 and acridinyl moieties.
abstract: Oxovanadium(iv) complexes of vitamin-B6 Schiff base, viz., [VO(HL(1)/L(2)/L(3))(B)]Cl (), where B is 2,2'-bipyridine (bpy in and ), 11-(9-acridinyl)dipyrido[3,2-a:2',3'-c]phenazine (acdppz in and ), H2L(1)·HCl is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-1-ium chloride (in and ), HL(2) is 2-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)phenol (in ) and HL(3) is 4-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (in ) were synthesized, characterized and their cellular uptake, photo-activated cytotoxicity and intracellular localization were studied. Complexes , as the perchlorate salt of , and , as the hexafluorophosphate salt of , were structurally characterized. Vitamin-B6 transporting membrane carrier (VTC) mediated entry into tumour cells in preference to the normal ones seems to be responsible for the higher cellular uptake of the complexes into HeLa and MCF-7 cells over MCF-10A cells. Complexes and having acdppz as the photosensitizer exhibit remarkable photocytotoxicity in these cancer cells giving IC50 of <0.9 μM. The complexes remain non-toxic in the dark. The complexes show photo-induced apoptotic cell death via singlet oxygen ((1)O2) generation. Fluorescence microscopy reveals specific localization of complex to endoplasmic reticulum (ER) and generation of (1)O2 possibly leads to apoptotic cell death by triggering ER stress response (ERSR).
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.
authors.forename: Samya
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India. anjali@biochem.iisc.ernet.in.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Dixit
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India. anjali@biochem.iisc.ernet.in.
authors.forename: Anjali A
authors.initials: AA
authors.lastname: Karande
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D008968:Molecular Conformation; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011789:Quantum Theory; D012545:Schiff Bases / Q000737:chemistry; D026082:Singlet Oxygen / Q000378:metabolism; D012995:Solubility; D014638:Vanadates / Q000737:chemistry*; D025101:Vitamin B 6 / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D017319:Photosensitizing Agents; D012545:Schiff Bases; D026082:Singlet Oxygen; D014638:Vanadates; D015082:2,2'-Dipyridyl; D025101:Vitamin B 6