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Impact of mono- and di-β-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy

To investigate the impact of mono- and di-β-galactose moieties in tumor uptake and photodynamic therapy (PDT) efficacy, HPPH [3-(1′-hexyloxy)ethyl-3-devinylpyropheophorobide-a], the meso pyropheophorbide-a [3-ethyl-3-devinyl-pyropheophorbide-a], and the corresponding 20-benzoic acid analogs were use...

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Autores principales: Dukh, Mykhaylo, Cacaccio, Joseph, Durrani, Farukh A., Kumar, Ishaan, Watson, Ramona, Tabaczynski, Walter A., Joshi, Penny, Missert, Joseph R., Baumann, Heinz, Pandey, Ravindra K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776133/
https://www.ncbi.nlm.nih.gov/pubmed/36568335
http://dx.doi.org/10.1016/j.ejmcr.2022.100047
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author Dukh, Mykhaylo
Cacaccio, Joseph
Durrani, Farukh A.
Kumar, Ishaan
Watson, Ramona
Tabaczynski, Walter A.
Joshi, Penny
Missert, Joseph R.
Baumann, Heinz
Pandey, Ravindra K.
author_facet Dukh, Mykhaylo
Cacaccio, Joseph
Durrani, Farukh A.
Kumar, Ishaan
Watson, Ramona
Tabaczynski, Walter A.
Joshi, Penny
Missert, Joseph R.
Baumann, Heinz
Pandey, Ravindra K.
author_sort Dukh, Mykhaylo
collection PubMed
description To investigate the impact of mono- and di-β-galactose moieties in tumor uptake and photodynamic therapy (PDT) efficacy, HPPH [3-(1′-hexyloxy)ethyl-3-devinylpyropheophorobide-a], the meso pyropheophorbide-a [3-ethyl-3-devinyl-pyropheophorbide-a], and the corresponding 20-benzoic acid analogs were used as starting materials. Reaction of the intermediates containing one or two carboxylic acid functionalities with 1-aminogalactose afforded the desired 17(2)- or 20(4′)- mono- and 17(2), 20(4′)-di galactose conjugated photosensitizers (PSs) with and without a carboxylic acid group. The overall lipophilicity caused by the presence of galactose in combination with either an ethyl or (1′-hexyloxy)ethyl side chain at position-3 of the macrocycle made a significant difference in in vitro uptake by tumor cells and photoreaction upon light exposure. Interestingly, among the PSs investigated, compared to HPPH 1 the carbohydrate conjugates 2 and 11 in which β-galactose moieties are conjugated at positions 17(2) and 20(4′) of meso-pyro pheophorbide-a showed similar in vitro efficacy in FaDu cell lines, but in SCID mice bearing FaDu tumors (head & neck) Ps 11 gave significantly improved long-term tumor cure.
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spelling pubmed-97761332022-12-22 Impact of mono- and di-β-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy Dukh, Mykhaylo Cacaccio, Joseph Durrani, Farukh A. Kumar, Ishaan Watson, Ramona Tabaczynski, Walter A. Joshi, Penny Missert, Joseph R. Baumann, Heinz Pandey, Ravindra K. Eur J Med Chem Rep Article To investigate the impact of mono- and di-β-galactose moieties in tumor uptake and photodynamic therapy (PDT) efficacy, HPPH [3-(1′-hexyloxy)ethyl-3-devinylpyropheophorobide-a], the meso pyropheophorbide-a [3-ethyl-3-devinyl-pyropheophorbide-a], and the corresponding 20-benzoic acid analogs were used as starting materials. Reaction of the intermediates containing one or two carboxylic acid functionalities with 1-aminogalactose afforded the desired 17(2)- or 20(4′)- mono- and 17(2), 20(4′)-di galactose conjugated photosensitizers (PSs) with and without a carboxylic acid group. The overall lipophilicity caused by the presence of galactose in combination with either an ethyl or (1′-hexyloxy)ethyl side chain at position-3 of the macrocycle made a significant difference in in vitro uptake by tumor cells and photoreaction upon light exposure. Interestingly, among the PSs investigated, compared to HPPH 1 the carbohydrate conjugates 2 and 11 in which β-galactose moieties are conjugated at positions 17(2) and 20(4′) of meso-pyro pheophorbide-a showed similar in vitro efficacy in FaDu cell lines, but in SCID mice bearing FaDu tumors (head & neck) Ps 11 gave significantly improved long-term tumor cure. 2022-08 2022-04-18 /pmc/articles/PMC9776133/ /pubmed/36568335 http://dx.doi.org/10.1016/j.ejmcr.2022.100047 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Dukh, Mykhaylo
Cacaccio, Joseph
Durrani, Farukh A.
Kumar, Ishaan
Watson, Ramona
Tabaczynski, Walter A.
Joshi, Penny
Missert, Joseph R.
Baumann, Heinz
Pandey, Ravindra K.
Impact of mono- and di-β-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy
title Impact of mono- and di-β-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy
title_full Impact of mono- and di-β-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy
title_fullStr Impact of mono- and di-β-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy
title_full_unstemmed Impact of mono- and di-β-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy
title_short Impact of mono- and di-β-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy
title_sort impact of mono- and di-β-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776133/
https://www.ncbi.nlm.nih.gov/pubmed/36568335
http://dx.doi.org/10.1016/j.ejmcr.2022.100047
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