5 research outputs found

    Synthesis of 5-Fluorouracil Cocrystals with Novel Organic Acids as Coformers and Anticancer Evaluation against HCT-116 Colorectal Cell Lines

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    5-Fluorouracil (5-FU) being a mainstream anticancer drug is under keen and detailed investigation for prodrugs formulations in order to minimize the associated side effects. Cocrystallization of 5-FU is an innovative technique for the synthesis of 5-FU prodrugs to improve its anticancer effectiveness. The present study is based on the synthesis of 5-FU supramolecular synthons with four coformers: succinic acid, cinnamic acid, malic acid, and benzoic acid utilizing acetone as a solvent. Solid state grinding followed by a slow evaporation solution method was applied. Colorless clear crystals were obtained in all the cases. The cocrystal formation was supported with the help of Fourier transform infrared (FTIR) spectroscopy and powder X-ray diffraction (PXRD). Through FTIR, the main peaks of interest in the spectrum of 5-FU were N–H (3409.02 cm–1) and carbonyl group (1647.80 cm–1), which were prominently shifted in all spectra of the cocrystals demonstrating the replacement as well as the development of already present interactions with the new ones. For 5-FU–cinnamic acid cocrystals, the anticipated peaks were observed at 1673.13 cm–1 (−C═O) and 3566.89 cm–1 (N–H) manifesting a significant change in comparison to 5-FU. Furthermore, with the help of PXRD characterization, the representative peak of 5-FU was recorded at 2θ = 28.80°. The shifting of this specific peak and development of many new ones in the spectra of cocrystals proved the development of new structural entities. Finally, the anticancer activity of all cocrystals was evaluated in comparison to that of API. All cocrystals manifest significantly greater growth inhibition potential than the main active pharmaceutical ingredient. 5-FU–Cinnamic acid (3C) was the one that proved to be the most potent anticancer agent at all four concentrations: 4.82% (12 μg/mL), 34.21% (25 μg/mL), 55.08% (50 μg/mL), and 67.29% (100 μg/mL). In short, this study proved to be a true example to enhance the anticancer potential of 5-FU following fairly easy fabrication requirements of the cocrystallization phenomenon. After the successful synthesis of these supramolecular synthons and subsequent enhancement of growth inhibition potential of 5-FU, these cocrystals can further be evaluated for in vivo trials and membrane crossing potentials in the future

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

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    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 Nsingle bondH absorption frequency was recorded at 3409.02 cm−1 and that of single bondCdouble bondO 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 Nsingle bondH and single bondCdouble bondO 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

    Development of biomass derived highly porous fast adsorbents for post-combustion CO2 capture

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    This study is carried out for a comparative screening of three groups of biomasses; soft or non-woody (peanut shell); intermediate woody (walnut shell) and hard woody (pine wood) for the development of adsorbents/activated carbons for post-combustion CO2 capture (over N2 balance). Three different groups of biomass residues are selected to study the role and nature of the material in adsorption and selection of the raw material for CO2 adsorbents synthesis for future researches because of the hot issue of anthropogenic CO2 emissions. The adsorption isotherms studied by the thermal gravimetric analyser (TGA) revealed that CO2 adsorption capabilities are in the range of 2.53–3.92 mmol/g (over N2 balance) at 25 °C. The newly synthesised activated carbons (ACs) exhibited a fast rate of adsorption as 41–94% in the initial 2 min. Porous surface development with catalytic KOH activation is seen clearly through SEM surface morphological analyses and mathematically confirmed from SBET ranges from 146.86 to 944.05 m2/g. FTIR and XRD peaks verify the generation of basic or inorganic O2-rich moieties that help in acidic CO2 capture. It has also been observed from adsorption isotherms that the order of higher adsorption groups is as; peanut shell > pine wood > walnut shell, while the best activation mass ratio (sample/KOH) is 1:3. The synthesised low cost ACs with an amount of 1.93 US$ per kg production could help to overcome the environmental hazards and problems caused by CO2 and biomass waste
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