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Issue 18, 2011
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Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative

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Abstract

A new water soluble cationic imidazopyridine species, viz. (1E)-1-((pyridin-2-yl)methyleneamino)-3-(3-(pyridin-2-yl)imidazo[1,5-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 (ϕ) 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+.

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

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Publication details

The article was received on 07 Dec 2010, accepted on 25 Feb 2011 and first published on 24 Mar 2011


Article type: Paper
DOI: 10.1039/C0DT01717E
Dalton Trans., 2011,40, 4855-4864

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

    M. Roy, B. V. S. K. Chakravarthi, C. Jayabaskaran, A. A. Karande and A. R. Chakravarty, Dalton Trans., 2011, 40, 4855
    DOI: 10.1039/C0DT01717E

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