Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil

Mustafa, Yasser Fakri; Oglah, Mahmood Khudhayer; Bashir, Moath Kahtan

Yasser Fakri Mustafa, Mahmood Khudhayer Oglah, Moath Kahtan Bashir

Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil

Abstract:

The oral use of 5-fluorouracil is being deserted in the last decades due to its atypical intestinal absorption, which is primarily attributed to the mutable activity of dihydropyrimidine dehydrogenase located in the gastrointestinal mucosa. In this work, a coumarin-based prodrug system was utilized to synthesize a novel mutual prodrug of 5-fluorouracil and 5-ethynyluracil. This prodrug was designed to afford a concurrent release of these two active drugs resulting in the improvement of the therapeutic efficacy of both. The synthetic pathway involved 7 linear steps starting from coumarin. The chemical structures of the intermediates and prodrug were established by analyzing their FTIR, 1H-NMR, and 13C-NMR spectra. The in vitro chemical stability of the synthesized prodrug was tested in the HCl buffer (pH 1.2) and phosphate-buffered saline (pH 6.8), while its ability to release the active moieties was studied in human serum. The outcomes of these in vitro studies revealed that the prodrug showed a significant stability in the HCl buffer and phosphate-buffered saline with half-lives of 33.19 h and 18.13 hr respectively, obeying pseudo-first-order kinetics. Also, the prodrug was able to release the two active components in human serum with a half-life of 4.62 h obeying zero-order kinetics. It is concluded that the synthesized prodrug represents a promising oral prodrug of 5-fluorouracil and 5-ethynyluracil to serve better in therapeutics.

Keywords:
Coumarin-based prodrug; 5-fluorouracil; 5-ethynyluracil; kinetics

Issue: 2020, Volume 71, Issue 12

Pages: 97-108

Publication date: 2021/1/7

https://doi.org/10.37358/RC.20.12.8390

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This article is published under the Creative Commons Attribution 4.0 International License

Citation Styles

Cite this article as:
MUSTAFA, Y.F., OGLAH, M.K., BASHIR, M.K., Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil, Rev. Chim., 71(12), 2020, 97-108.

Vancouver
Mustafa YF, Oglah MK, Bashir MK. Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil. Rev. Chim.[internet]. 2020 Dec;71(12):97-108. Available from: https://doi.org/10.37358/RC.20.12.8390

APA 6th edition
Mustafa, Y.F., Oglah, M.K. & Bashir, M.K. (2020). Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil. Revista de Chimie, 71(12), 97-108. https://doi.org/10.37358/RC.20.12.8390

Harvard
Mustafa, Y.F., Oglah, M.K., Bashir, M.K. (2020). 'Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil', Revista de Chimie, 71(12), pp. 97-108. https://doi.org/10.37358/RC.20.12.8390

IEEE
Y.F. Mustafa, M.K. Oglah, M.K. Bashir, "Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil". Revista de Chimie, vol. 71, no. 12, pp. 97-108, 2020. [online]. https://doi.org/10.37358/RC.20.12.8390

Text
Yasser Fakri Mustafa, Mahmood Khudhayer Oglah, Moath Kahtan Bashir,
Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil,
Revista de Chimie,
Volume 71, Issue 12,
2020,
Pages 97-108,
ISSN 2668-8212,
https://doi.org/10.37358/RC.20.12.8390.
(https://revistadechimie.ro/Articles.asp?ID=8390)
Keywords: Coumarin-based prodrug; 5-fluorouracil; 5-ethynyluracil; kinetics

RIS
TY - JOUR
T1 - Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil
A1 - Mustafa, Yasser Fakri
A2 - Oglah, Mahmood Khudhayer
A3 - Bashir, Moath Kahtan
JF - Revista de Chimie
JO - Rev. Chim.
PB - Revista de Chimie SRL
SN - 2668-8212
Y1 - 2020
VL - 71
IS - 12
SP - 97
EP - 108
UR - https://doi.org/10.37358/RC.20.12.8390
KW - Coumarin-based prodrug
KW - 5-fluorouracil
KW - 5-ethynyluracil
KW - kinetics
ER -

BibTex
@article{RevCh2020P97,
author = {Mustafa Yasser Fakri and Oglah Mahmood Khudhayer and Bashir Moath Kahtan},
title = {Synthesis and Kinetic Study of Novel Coumarin- Based Mutual Prodrug of 5-fluorouracil and 5-ethynyluracil},
journal = {Revista de Chimie},
volume = {71},
number = {12},
pages = {97-108},
year = {2020},
issn = {2668-8212},
doi = {https://doi.org/10.37358/RC.20.12.8390},
url = {https://revistadechimie.ro/Articles.asp?ID=8390}
}

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