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Formulation, characterization, cytotoxicity and Salmonella/microsome mutagenicity (Ames) studies of a novel 5-fluorouracil derivative

5-Fluorouracil is one of the first line drugs for the systemic therapy of solid tumors like breast, colorectal, oesophageal, stomach, pancreatic, head and neck. It could be shown that sugars can improve the absorption across cell membranes and can help to bypass some pharmacokinetic problems. Carboh...

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Autores principales: Köksal Karayildirim, Çinel, Kotmakçi, Mustafa, Halay, Erkan, Ay, Kadir, Başpinar, Yücel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856941/
https://www.ncbi.nlm.nih.gov/pubmed/29556128
http://dx.doi.org/10.1016/j.jsps.2018.01.004
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author Köksal Karayildirim, Çinel
Kotmakçi, Mustafa
Halay, Erkan
Ay, Kadir
Başpinar, Yücel
author_facet Köksal Karayildirim, Çinel
Kotmakçi, Mustafa
Halay, Erkan
Ay, Kadir
Başpinar, Yücel
author_sort Köksal Karayildirim, Çinel
collection PubMed
description 5-Fluorouracil is one of the first line drugs for the systemic therapy of solid tumors like breast, colorectal, oesophageal, stomach, pancreatic, head and neck. It could be shown that sugars can improve the absorption across cell membranes and can help to bypass some pharmacokinetic problems. Carbohydrates as most common organic molecules are an important issue of plant and animal metabolisms. They are non toxic and have important duties in the body like participating in DNA and RNA synthesis and being responsible for energy production. In addition, they have many hydroxyl, aldehyde and ketone groups that attract attention for synthesis as a potential drug derivative. 1,2,3,-Triazole compounds have also important role in heterocyclic chemistry because of their pharmaceutical properties and their high reactivity, which could be used as a building block for complex chemical compounds. In this study, following the “Click Reaction” of 5-FU and tetra-O-acetylglycose the 5-fluorouracil derivative 1-[{1′-(2″,3″,4″,6″-tetra-O-acetyl-β-d-glycopyronosyl)-1′H-1′,2′,3′-triazole-4′-yl} methyl]5-fluorouracil was synthesized. Following, a micellar formulation of 5-Fluorouracil derivative was prepared and characterized in terms of particle size, polydispersity index, zeta potential, refractive index and pH. Furthermore, the cytotoxicity and mutagenicity of the 5-fluorouracil derivative was investigated using an in vitro cell culture model and the AMES test. According to the results of this study, the novel 5-fluorouracil derivative could be a drug candidate for the therapy of cancer and needs further in vivo investigations.
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spelling pubmed-58569412018-03-19 Formulation, characterization, cytotoxicity and Salmonella/microsome mutagenicity (Ames) studies of a novel 5-fluorouracil derivative Köksal Karayildirim, Çinel Kotmakçi, Mustafa Halay, Erkan Ay, Kadir Başpinar, Yücel Saudi Pharm J Article 5-Fluorouracil is one of the first line drugs for the systemic therapy of solid tumors like breast, colorectal, oesophageal, stomach, pancreatic, head and neck. It could be shown that sugars can improve the absorption across cell membranes and can help to bypass some pharmacokinetic problems. Carbohydrates as most common organic molecules are an important issue of plant and animal metabolisms. They are non toxic and have important duties in the body like participating in DNA and RNA synthesis and being responsible for energy production. In addition, they have many hydroxyl, aldehyde and ketone groups that attract attention for synthesis as a potential drug derivative. 1,2,3,-Triazole compounds have also important role in heterocyclic chemistry because of their pharmaceutical properties and their high reactivity, which could be used as a building block for complex chemical compounds. In this study, following the “Click Reaction” of 5-FU and tetra-O-acetylglycose the 5-fluorouracil derivative 1-[{1′-(2″,3″,4″,6″-tetra-O-acetyl-β-d-glycopyronosyl)-1′H-1′,2′,3′-triazole-4′-yl} methyl]5-fluorouracil was synthesized. Following, a micellar formulation of 5-Fluorouracil derivative was prepared and characterized in terms of particle size, polydispersity index, zeta potential, refractive index and pH. Furthermore, the cytotoxicity and mutagenicity of the 5-fluorouracil derivative was investigated using an in vitro cell culture model and the AMES test. According to the results of this study, the novel 5-fluorouracil derivative could be a drug candidate for the therapy of cancer and needs further in vivo investigations. Elsevier 2018-03 2018-01-10 /pmc/articles/PMC5856941/ /pubmed/29556128 http://dx.doi.org/10.1016/j.jsps.2018.01.004 Text en © 2018 The Authors http://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/).
spellingShingle Article
Köksal Karayildirim, Çinel
Kotmakçi, Mustafa
Halay, Erkan
Ay, Kadir
Başpinar, Yücel
Formulation, characterization, cytotoxicity and Salmonella/microsome mutagenicity (Ames) studies of a novel 5-fluorouracil derivative
title Formulation, characterization, cytotoxicity and Salmonella/microsome mutagenicity (Ames) studies of a novel 5-fluorouracil derivative
title_full Formulation, characterization, cytotoxicity and Salmonella/microsome mutagenicity (Ames) studies of a novel 5-fluorouracil derivative
title_fullStr Formulation, characterization, cytotoxicity and Salmonella/microsome mutagenicity (Ames) studies of a novel 5-fluorouracil derivative
title_full_unstemmed Formulation, characterization, cytotoxicity and Salmonella/microsome mutagenicity (Ames) studies of a novel 5-fluorouracil derivative
title_short Formulation, characterization, cytotoxicity and Salmonella/microsome mutagenicity (Ames) studies of a novel 5-fluorouracil derivative
title_sort formulation, characterization, cytotoxicity and salmonella/microsome mutagenicity (ames) studies of a novel 5-fluorouracil derivative
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856941/
https://www.ncbi.nlm.nih.gov/pubmed/29556128
http://dx.doi.org/10.1016/j.jsps.2018.01.004
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