Synthesis and bioassay studies of cationic porphyrins for gene transfection delivery

Porphyrins are stable aromatic tetrapyrrolic macromolecules found in many natural products such as hemin, chlorophylls and vitamin B12. Interaction ability of cationic porphyrins with nucleic acid and their fluorescent properties for location identification in cellular domain have promoted their use...

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Main Author:	Kiew, Siaw Fui
Format:	Thesis
Language:	English
Published:	2013
Subjects:	QD Chemistry
Online Access:	http://eprints.utm.my/id/eprint/33842/1/KiewSiawFuiMFS2013.pdf
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spelling	my-utm-ep.338422017-07-18T02:12:13Z Synthesis and bioassay studies of cationic porphyrins for gene transfection delivery 2013 Kiew, Siaw Fui QD Chemistry Porphyrins are stable aromatic tetrapyrrolic macromolecules found in many natural products such as hemin, chlorophylls and vitamin B12. Interaction ability of cationic porphyrins with nucleic acid and their fluorescent properties for location identification in cellular domain have promoted their uses as potential gene vectors for gene therapy. In this study, basic cationic porphyrins bearing four positive charges were synthesized. Besides, amphiphilic porphyrins anchored with both hydrophobic and hydrophilic moieties were prepared to facilitate membrane penetration and to give a higher cellular uptake. Polyamidoamine(PAMAM)-porphyrin conjugate was also prepared to produce a complex with higher transfection level but with low toxicity. Adler-Longo condensation method was mainly used to synthesize these cationic porphyrin precursors. All cationic porphyrins were obtained in high yield. All of the compounds were characterized using 1H-NMR, 13C-NMR, ultraviolet (UV) and infrared(IR) spectroscopies.Cytotoxicity and cellular uptake of all cationic compounds were tested on Chinese Hamster Ovary (CHO) cells to evaluate their potential uses as gene carriers. Results revealed that all porphyrins show relatively low toxicity towards the cell even at high concentration(100 μM).The 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin and two amphiphilic cationic porphyrins of 5-hexyl-10,15,20-tris(N-methyl-4-pyridyl) porphyrin and 5-propyl-10,15,20-tris(N-methyl-4-pyridyl)porphyrin which contain three positive charges on the periphery show the highest cellular uptake. It was also found that the amphiphilic cis-porphyrins of 5,10-dipropyl-15,20-bis(N-methyl-4-pyridyl)porphyrin and 5,10-dihexyl-15,20-bis(N-methyl-4-pyridyl)porphyrin exhibited higher cellular uptake compared to their trans-isomers, 5,15-dipropyl-10,20-bis(N-methyl-4-pyridyl)porphyrin and 5,15-dihexyl-10,20-bis(N-methyl-4- pyridyl)porphyrin. 2013 Thesis http://eprints.utm.my/id/eprint/33842/ http://eprints.utm.my/id/eprint/33842/1/KiewSiawFuiMFS2013.pdf application/pdf en public http://dms.library.utm.my:8080/vital/access/manager/Repository/vital:72933?queryType=vitalDismax&query=+Synthesis+and+bioassay+studies+of+cationic+porphyrins+for+gene+transfection+delivery&public=true masters Universiti Teknologi Malaysia, Faculty of Science Faculty of Science
institution	Universiti Teknologi Malaysia
collection	UTM Institutional Repository
language	English
topic	QD Chemistry
spellingShingle	QD Chemistry Kiew, Siaw Fui Synthesis and bioassay studies of cationic porphyrins for gene transfection delivery
description	Porphyrins are stable aromatic tetrapyrrolic macromolecules found in many natural products such as hemin, chlorophylls and vitamin B12. Interaction ability of cationic porphyrins with nucleic acid and their fluorescent properties for location identification in cellular domain have promoted their uses as potential gene vectors for gene therapy. In this study, basic cationic porphyrins bearing four positive charges were synthesized. Besides, amphiphilic porphyrins anchored with both hydrophobic and hydrophilic moieties were prepared to facilitate membrane penetration and to give a higher cellular uptake. Polyamidoamine(PAMAM)-porphyrin conjugate was also prepared to produce a complex with higher transfection level but with low toxicity. Adler-Longo condensation method was mainly used to synthesize these cationic porphyrin precursors. All cationic porphyrins were obtained in high yield. All of the compounds were characterized using 1H-NMR, 13C-NMR, ultraviolet (UV) and infrared(IR) spectroscopies.Cytotoxicity and cellular uptake of all cationic compounds were tested on Chinese Hamster Ovary (CHO) cells to evaluate their potential uses as gene carriers. Results revealed that all porphyrins show relatively low toxicity towards the cell even at high concentration(100 μM).The 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin and two amphiphilic cationic porphyrins of 5-hexyl-10,15,20-tris(N-methyl-4-pyridyl) porphyrin and 5-propyl-10,15,20-tris(N-methyl-4-pyridyl)porphyrin which contain three positive charges on the periphery show the highest cellular uptake. It was also found that the amphiphilic cis-porphyrins of 5,10-dipropyl-15,20-bis(N-methyl-4-pyridyl)porphyrin and 5,10-dihexyl-15,20-bis(N-methyl-4-pyridyl)porphyrin exhibited higher cellular uptake compared to their trans-isomers, 5,15-dipropyl-10,20-bis(N-methyl-4-pyridyl)porphyrin and 5,15-dihexyl-10,20-bis(N-methyl-4- pyridyl)porphyrin.
format	Thesis
qualification_level	Master's degree
author	Kiew, Siaw Fui
author_facet	Kiew, Siaw Fui
author_sort	Kiew, Siaw Fui
title	Synthesis and bioassay studies of cationic porphyrins for gene transfection delivery
title_short	Synthesis and bioassay studies of cationic porphyrins for gene transfection delivery
title_full	Synthesis and bioassay studies of cationic porphyrins for gene transfection delivery
title_fullStr	Synthesis and bioassay studies of cationic porphyrins for gene transfection delivery
title_full_unstemmed	Synthesis and bioassay studies of cationic porphyrins for gene transfection delivery
title_sort	synthesis and bioassay studies of cationic porphyrins for gene transfection delivery
granting_institution	Universiti Teknologi Malaysia, Faculty of Science
granting_department	Faculty of Science
publishDate	2013
url	http://eprints.utm.my/id/eprint/33842/1/KiewSiawFuiMFS2013.pdf
_version_	1747816198525943808

Synthesis and bioassay studies of cationic porphyrins for gene transfection delivery

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