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Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative

Roy, Mithun and Chakravarthi, Balabhadrapatruni VSK and Jayabaskaran, Chelliah and Karande, Anjali A and Chakravarty, Akhil R (2011) Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative. In: 1477-9226 , 40 (18). pp. 4855-4864.

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Abstract

A new water soluble cationic imidazopyridine species, viz. (1E)-1-((pyridin-2-yl)methyleneamino)-3-(3(pyridin-2-yl) imidazo1,5-a]pyridin-2(3H)-yl)propan-2-ol (1), as a metal chelator is prepared as its PF6 salt and characterized. Compound 1 shows fluorescence at 438 nm on excitation at 342 nm in Tris-HCl buffer giving a fluorescence quantum yield (phi) of 0.105 and a life-time of 5.4 ns. Compound 1, as an avid DNA minor groove binder, shows pUC19 DNA cleavage activity in UV-A light of 365 nm forming singlet oxygen species in a type-II pathway. The photonuclease potential of 1 gets enhanced in the presence of Fe2+, Cu2+ or Zn2+. Compound 1 itself displays anticancer activity in HeLa, HepG2 and Jurkat cells with an enhancement on addition of the metal ions. Photodynamic effect of 1 at 365 nm also gets enhanced in the presence of Fe2+ and Zn2+. Fluorescence-based cell cycle analysis shows a significant dead cell population in the sub-G1 phase of the cell cycle suggesting apoptosis via ROS generation. A significant change in the nuclear morphology is observed from Hoechst 33258 and an acridine orange/ethidium bromide (AO/EB) dual nuclear staining suggesting apoptosis in cells when treated with 1 alone or in the presence of the metal ions. Apoptosis is found to be caspase-dependent. Fluorescence imaging to monitor the distribution of 1 in cells shows that 1 in the presence of metal ions accumulates predominantly in the cytoplasm. Enhanced uptake of 1 into the cells within 12 h is observed in the presence of Fe2+ and Zn2+.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Royal Society of Chemistry.
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Chemical Sciences > Inorganic & Physical Chemistry
Depositing User: Id for Latest eprints
Date Deposited: 20 May 2011 07:07
Last Modified: 20 May 2011 07:07
URI: http://eprints.iisc.ac.in/id/eprint/37688

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