Endoplasmic reticulum targeting tumour selective photocytotoxic oxovanadium(IV) complexes having vitamin-B6 and acridinyl moieties


Autoria(s): Banerjee, Samya; Dixit, Akanksha; Karande, Anjali A; Chakravarty, Akhil R
Data(s)

2016

Resumo

Oxovanadium(IV) complexes of vitamin-B6 Schiff base, viz., VO(HL1/L-2/L-3)(B)] Cl (1-4), where B is 2,2'-bipyridine (bpy in 1 and 2), 11-(9-acridinyl)dipyrido3,2-a:2',3'-c]phenazine (acdppz in 3 and 4), H2L1 center dot HCl is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylp yridin-1-ium chloride (in 1 and 4), HL2 is 2-(((2-(1H-imidazol-4-yl)ethyl) imino)methyl) phenol (in 2) and HL3 is 4-(((2-(1H-imidazol-4- yl)ethyl)imino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (in 3) were synthesized, characterized and their cellular uptake, photo-activated cytotoxicity and intracellular localization were studied. Complexes 1a, as the perchlorate salt of 1, and 2a, as the hexafluorophosphate salt of 2, were structurally characterized. Vitamin-B6 transporting membrane carrier (VTC) mediated entry into tumour cells in preference to the normal ones seems to be responsible for the higher cellular uptake of the complexes into HeLa and MCF-7 cells over MCF-10A cells. Complexes 3 and 4 having acdppz as the photosensitizer exhibit remarkable photocytotoxicity in these cancer cells giving IC50 of < 0.9 mu M. The complexes remain non-toxic in the dark. The complexes show photo-induced apoptotic cell death via singlet oxygen (O-1(2)) generation. Fluorescence microscopy reveals specific localization of complex 4 to endoplasmic reticulum (ER) and generation of O-1(2) possibly leads to apoptotic cell death by triggering ER stress response (ERSR).

Formato

application/pdf

Identificador

http://eprints.iisc.ernet.in/53199/1/Dal_Tra_45-2_783_2016.pdf

Banerjee, Samya and Dixit, Akanksha and Karande, Anjali A and Chakravarty, Akhil R (2016) Endoplasmic reticulum targeting tumour selective photocytotoxic oxovanadium(IV) complexes having vitamin-B6 and acridinyl moieties. In: DALTON TRANSACTIONS, 45 (2). pp. 783-796.

Publicador

ROYAL SOC CHEMISTRY

Relação

http://dx.doi.org/10.1039/c5dt03412d

http://eprints.iisc.ernet.in/53199/

Palavras-Chave #Biochemistry #Inorganic & Physical Chemistry
Tipo

Journal Article

PeerReviewed