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

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 N—H 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 N—H 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.

Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction

“…XRD patterns of pure 5FU, and PU and PU 5FU coatings were recorded ( Figure 3 ) and d -spacing values were determined for prominent peaks ( SI, Table S4 ). Pure 5FU revealed a series of characteristic diffraction peaks consistent with those reported previously [ 42 , 56 , 59 , 61 , 69 , 70 ], with a prominent 2 θ peak at 28.6° corresponding to a d -spacing of 3.123 Å. The diffractogram of the PU coating revealed a broad 2 θ peak at 19.9° and a low intensity 2 θ peak at 29.2°, which are consistent with previous literature reports and can be attributed to amorphous and semicrystalline segmented polycarbonate-PUs [ 43 , 71 , 72 ].…”

“…The 2 θ peak at 28.1° ( d -space = 3.182 Å) in the PU 5FU coating was very similar to the dominant 5FU peak (28.6°) and was attributed to the presence of 5FU crystallites within the PU matrix. Broadening of this peak may also be indicative of slight changes in the regular crystalline structure of 5FU or intermolecular interactions with the PU matrix [ 70 ]. The decrease in the intensity (28-fold) of the 5FU peaks in the PU matrix compared to the free-drug is unlikely to result from dilution alone, and probably also corresponds to the presence of less and smaller 5FU crystallites [ 70 ].…”

“…Broadening of this peak may also be indicative of slight changes in the regular crystalline structure of 5FU or intermolecular interactions with the PU matrix [ 70 ]. The decrease in the intensity (28-fold) of the 5FU peaks in the PU matrix compared to the free-drug is unlikely to result from dilution alone, and probably also corresponds to the presence of less and smaller 5FU crystallites [ 70 ]. These observations indicate that the majority of 5FU in the PU matrix is in amorphous state along with a small proportion of crystalline drug.…”

CRISPR/Cas9: A powerful genome editing technique for the treatment of cancer cells with present challenges and future directions

“…During the past few decades, different therapies, including immunotherapy, targeted antibodies, hormone therapy, chemotherapy, targeted drug therapy, stem cell transplant, and surgery have been introduced into the medical field for the betterment of prognosis in cancer patients, which significantly eradicate or condense the cancerous cells and upsurges the maximum lifespan of about only five years [ 4 , 5 ]. Even after these therapies, cancer continues to evolve and ultimately give rise to molecular heterogeneity attributed to various molecular events like epigenetic, genetic, phenotypic, and transcriptomic alternations.…”

New insights on possible vaccine development against SARS-CoV-2

“…But some preventive measures and compounds are showing better results to control the effects of coronavirus. Recently, different therapeutic strategies including remdesivir, lopinavir, hydroquinone, and dexamethasone are showing somehow better results but still are not admirable due to dose and time-dependent, increase in AST and ALT levels, decrease in the level of electrolytes, vomiting, and digestive disorders among patients [ [22] , [23] , [24] , [25] ]. Recently different developments have been done to develop vaccines against COVID-19.…”