Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents

Farhat Jubeen, Aisha Liaqat, Misbah Sultan, Sania Zafar Iqbal, Imran Sajid, Farooq Sher

Research output: Contribution to journalArticle

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Abstract

This study reports the formation of 5-FU co-crystals with four different pharmacologically safe co-formers; Urea, Thiourea, Acetanilide and Aspirin using methanol as a solvent. Two fabrication schemes were followed i.e., solid-state grinding protocol, in which API and co-formers were mixed through vigorous grinding while in the other method separate solutions of both the components were made and mixed together. The adopted approaches offer easy fabrication protocols, no temperature maintenance requirements, no need of expensive solvents, hardly available apparatus, isolation and purification of the desired products. In addition, there is no byproducts formation, In fact, a phenomenon embracing the requirements of green synthesis. Through FTIR analysis; for API the NH absorption frequency was recorded at 3409.02 cm−1 and that of CO was observed at 1647.77 cm−1. These characteristics peaks of 5-FU were significantly shifted and recorded at 3499.40 cm−1 and 1649.62 cm−1 for 5-FU-Ac (3B) and 3496.39 cm−1 and 1659.30 cm−1 for 5-FU-As (4B) co-crystals for NH and CO groups respectively. The structural differences between API and co-crystals were further confirmed through PXRD analysis. The characteristic peak of 5-FU at 2θ = 28.79918o was significantly shifted in the graphs of co-crystals not only in position but also with respect to intensity and FWHM values. In addition, new peaks were also recorded in all the spectra of co-formers confirming the structural differences between API and co-formers. In addition, percent growth inhibition was also observed by all the co-crystals through MTT assay against HCT 116 colorectal cell lines in vitro. At four different concentrations; 25, 50, 100 and 200 µg/mL, slightly different trends of the effectiveness of API and co-crystals were observed. However; among all the co-crystal forms, 5-FU-thiourea co-crystals obtained through solution method (2B) proved to be the most effective growth inhibitor at all the four above mentioned concentrations.
Original languageEnglish
Pages (from-to)1164-1173
Number of pages10
JournalSaudi Pharmaceutical Journal
Volume27
Issue number8
Early online date31 Oct 2019
DOIs
Publication statusPublished - 1 Dec 2019

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Fluorouracil
Antineoplastic Agents
Thiourea
Carbon Monoxide
HCT116 Cells
Growth Inhibitors
Fourier Transform Infrared Spectroscopy
Aspirin
Methanol
Urea
Maintenance
Cell Line
Temperature
Growth

Bibliographical note

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords

  • 5-Fluorouracil
  • Co-crystals
  • Green synthesis
  • Supramolecular interactions
  • Grinding and solution method

Cite this

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents. / Jubeen, Farhat; Liaqat, Aisha; Sultan, Misbah; Iqbal, Sania Zafar; Sajid, Imran; Sher, Farooq.

In: Saudi Pharmaceutical Journal, Vol. 27, No. 8, 01.12.2019, p. 1164-1173.

Research output: Contribution to journalArticle

Jubeen, Farhat ; Liaqat, Aisha ; Sultan, Misbah ; Iqbal, Sania Zafar ; Sajid, Imran ; Sher, Farooq. / Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents. In: Saudi Pharmaceutical Journal. 2019 ; Vol. 27, No. 8. pp. 1164-1173.
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N2 - This study reports the formation of 5-FU co-crystals with four different pharmacologically safe co-formers; Urea, Thiourea, Acetanilide and Aspirin using methanol as a solvent. Two fabrication schemes were followed i.e., solid-state grinding protocol, in which API and co-formers were mixed through vigorous grinding while in the other method separate solutions of both the components were made and mixed together. The adopted approaches offer easy fabrication protocols, no temperature maintenance requirements, no need of expensive solvents, hardly available apparatus, isolation and purification of the desired products. In addition, there is no byproducts formation, In fact, a phenomenon embracing the requirements of green synthesis. Through FTIR analysis; for API the NH absorption frequency was recorded at 3409.02 cm−1 and that of CO was observed at 1647.77 cm−1. These characteristics peaks of 5-FU were significantly shifted and recorded at 3499.40 cm−1 and 1649.62 cm−1 for 5-FU-Ac (3B) and 3496.39 cm−1 and 1659.30 cm−1 for 5-FU-As (4B) co-crystals for NH and CO groups respectively. The structural differences between API and co-crystals were further confirmed through PXRD analysis. The characteristic peak of 5-FU at 2θ = 28.79918o was significantly shifted in the graphs of co-crystals not only in position but also with respect to intensity and FWHM values. In addition, new peaks were also recorded in all the spectra of co-formers confirming the structural differences between API and co-formers. In addition, percent growth inhibition was also observed by all the co-crystals through MTT assay against HCT 116 colorectal cell lines in vitro. At four different concentrations; 25, 50, 100 and 200 µg/mL, slightly different trends of the effectiveness of API and co-crystals were observed. However; among all the co-crystal forms, 5-FU-thiourea co-crystals obtained through solution method (2B) proved to be the most effective growth inhibitor at all the four above mentioned concentrations.

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