Mitochondria-Targeting Photocytotoxic Ferrocenyl Conjugates of N-Alkylpyridinium Salts
Data(s) |
2015
|
---|---|
Resumo |
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. |
Formato |
application/pdf |
Identificador |
http://eprints.iisc.ernet.in/51378/1/eur_jou_ino_che-8_1398_2015.pdf 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. |
Publicador |
WILEY-V C H VERLAG GMBH |
Relação |
http://dx.doi.org/10.1002/ejic.201403118 http://eprints.iisc.ernet.in/51378/ |
Palavras-Chave | #Biochemistry #Inorganic & Physical Chemistry |
Tipo |
Journal Article PeerReviewed |