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|Title:||Effect of alkyl substituents on the photosensitizing activity of Zn(II) N-alkylpyridyl-porphyrins||Authors:||Monther Ghazal منذر عدنان غزال||Supervisor:||د. جيمس كريك||Keywords:||photodynamic therapy (PDT), photosensitizers, n-metalloalkylpyridylporphyrins||Issue Date:||2011||Publisher:||Kuwait university - college of graduate studies||Abstract:||The success of photodynamic therapy (PDT), as a minimally invasive approach, in treating both neoplastic and non-neoplastic diseases has stimulated the search for new photosensitizer compounds with potential application in PDT. It has previously been shown that Zn(II) N-methyl-porphyrins (ZnTM-2-PyP) can act as photosensitizers and kill human carcinoma cells and antibiotic-resistant bacteria. It is expected that increasing the hydrophobicity of the photosensitizing molecules will facilitate their cellular uptake, and thus increase their efficacy as photosensitizers. To test this idea N-butyl and N-hexyl analogs have been synthesized. The aim of the present study was to investigate their photosensitizing activity on eukaryotic cells. The ability of Zn(II) N-alkylpyridylporphyrins to induce photodynamic damage was tested on a human adenocarcinoma cultured cell line, LS174T. Dark and photo-induced toxicity of Zn(II) N-alkylpyridylporphyrins were demonstrated by trypan blue exclusion and MTT reduction tests. Mechanisms of photo-induced protein damage were investigated using purified proteins and isolated cell membrane preparations. The study showed that more lipophilic Zn-metalloalkylpyridylporphyrins gained enhanced photo-cytotoxicity without increased dark toxicity towards cultured cells. These agents caused photo-dependent loss of membrane barrier function and were more efficient in photo-modification of membrane proteins than the widely studied photosensitizer hematoporphyrin D (HpD). Protein cross-linking activity was reduced, but not abolished, by presence of singlet oxygen scavengers and these metalloalkylpyridylporphyrins showed capacity for photo-dependent cross-linking of membrane proteins under hypoxic conditions. These novel lipophilic photosensitizers show potential for future application in PDT.||URI:||http://hdl.handle.net/123456789/189|
|Appears in Programs:||0540 Medical Biochemistry (M.Sc.)|
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