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Mitochondria-Targeting Photocytotoxic Ferrocenyl Conjugates of N-Alkylpyridinium Salts

Balaji, Babu and Balakrishnan, Babita and Perumalla, Sravanakumar and Karande, Anjali A and Chakravarty, Akhil R (2015) Mitochondria-Targeting Photocytotoxic Ferrocenyl Conjugates of N-Alkylpyridinium Salts. In: EUROPEAN JOURNAL OF INORGANIC CHEMISTRY (8). pp. 1398-1407.

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Official URL: http://dx.doi.org/10.1002/ejic.201403118


Ferrocenyl (Fc) conjugates (1-3) of alkylpyridinium cations (E)-N-alkyl-4-2-(ferrocenyl)vinyl]pyridinium bromide (alkyl = n-butyl in 1, N,N,N-triethylbutan-1-aminium bromide in 2, and n-butyltriphenylphosphonium bromide in 3) were prepared and characterized, and their photocytotoxicities and cellular uptakes in HeLa cancer and 3T3 normal cells were studied. The species with a 4-methoxyphenyl moiety (4) instead of Fc was used as a control. The triphenylphosphonium-appended 3 was designed for specific delivery into the mitochondria of the cells. Compounds 1-3 showed metal-to-ligand charge-transfer bands at approximate to 550 nm in phosphate buffered saline (PBS). The Fc(+)/Fc and pyridinium core redox couples were observed at 0.75 and -1.2 V versus a saturated calomel electrode (SCE) in CH2Cl2/0.1 M (nBu(4)N)ClO4. Conjugate 3 showed a significantly higher photocytotoxicity in HeLa cancer cells IC50 = (1.3 +/- 0.2) M] than in normal 3T3 cells IC50 = (27.5 +/- 1.5) M] in visible light (400-700 nm). The positive role of the Fc moiety in 3 was evident from the inactive nature of 4. A JC-1 dye (5,5,6,6-tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide) assay showed that 3 targets the mitochondria and induces apoptosis by the mitochondrial intrinsic pathway caused by reactive oxygen species (ROS). Annexin/propidium iodide studies showed that 3 induces apoptotic cell death in visible light by ROS generation, as evidenced from dichlorofluorescein diacetate assay. Compounds 1-3 exhibit DNA photocleavage activity through the formation of hydroxyl radicals.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the WILEY-V C H VERLAG GMBH, BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
Keywords: Sandwich complexes; Medicinal chemistry; Anticancer agents; Cytotoxicity; Apoptosis
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited: 24 Apr 2015 05:48
Last Modified: 24 Apr 2015 05:48
URI: http://eprints.iisc.ac.in/id/eprint/51378

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