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Biotin-conjugated tumour-targeting photocytotoxic iron(III) complexes

Saha, Sounik and Majumdar, Ritankar and Hussain, Akhtar and Dighe, Rajan R and Chakravarty, Akhil R (2013) Biotin-conjugated tumour-targeting photocytotoxic iron(III) complexes. In: Philosophical Transactions of the Royal Society A-Mathematical Physical and Engineering Sciences, 371 (1995). 20120190_1-20120190_15.

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Official URL: http://dx.doi.org/10.1098/rsta.2012.0190

Abstract

Iron(III) complexes FeL(B)] (1-4) of a tetradentate phenolate-based ligand (H3L) and biotin-conjugated dipyridophenazine bases (B), viz. 7-aminodipyrido 3,2-a: 2',3'-c]-phenazine (dppza in 1), (N-dipyrido3,2-a: 2',3'-c]-phenazino) amidobiotin (dppzNB in 2), dipyrido 3,2-a: 2',3'-c]-phenazine-11-carboxylic acid (dppzc in 3) and 2-((2-biotinamido) ethyl) amidodipyrido 3,2-a: 2',3'-c]-phenazine (dppzCB in 4) are prepared, characterized and their interaction with streptavidin and DNA and their photocytotoxicity and cellular uptake in various cells studied. The high-spin iron(III) complexes display Fe(III)/Fe(II) redox couple near -0.7V versus saturated calomel electrode in dimethyl sulfoxide-0.1M tetrabutylammonium perchlorate. The complexes show non-specific interaction with DNA as determined from the binding studies. Complexes with appended biotin moiety show similar binding to streptavidin as that of free biotin, suggesting biotin conjugation to dppz does not cause any loss in its binding affinity to streptavidin. The photocytotoxicity of the complexes is tested in HepG2, HeLa and HEK293 cell lines. Complex 2 shows higher photocytotoxicity in HepG2 cells than in HeLa or HEK293, forming reactive oxygen species. This effect is attributed to the presence of overexpressed sodium-dependent multi-vitamin transporters in HepG2 cells. Microscopic studies in HepG2 cells show internalization of the biotin complexes 2 and 4 essentially occurring by receptor-mediated endocytosis, which is similar to that of native biotin and biotin fluorescein isothiocyanate conjugate.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Royal Society.
Keywords: Iron; Dipyridophenazine Biotin Conjugates; Streptavidin Binding; Photocytotoxicity; Cellular Uptake; Reactive Oxygen Species
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Division of Chemical Sciences > Inorganic & Physical Chemistry
Depositing User: Francis Jayakanth
Date Deposited: 05 Aug 2013 11:47
Last Modified: 05 Aug 2013 11:47
URI: http://eprints.iisc.ac.in/id/eprint/46899

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