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

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

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

Risk Assessment of Hepatocellular Carcinoma with Aflatoxin B1 Exposure in Edible Oils

Contamination of edible oils with aflatoxins (AFs) is a universal issue due to the detrimental effects of aflatoxins on human health and the fact that edible oils are a major source of fungal growth, particularly storage fungi (Aspergillus sp.). The objective of this study was to assess aflatoxin B1 (AFB1) in edible oil used in fried food in order to determine the risk of cancer from AFB1 exposure through cooked food using the FAO/WHO’s and EFSA’s margin of exposure (MOE) quantitative liver cancer risk approaches. Using Mycosep 226 columns and HPLC-FLD, 100 samples of cooking oils (soybean, canola, and sunflower oil) from different food points were analyzed for contamination with aflatoxins. Of all the samples tested, 89% were positive for total aflatoxins and AFB1, with 65% indicating AF concentrations beyond permitted levels. Canola oil was found to contain higher levels of AFB1 and AFs than soybean and sunflower oil. Almost 71 percent of canola oil samples (range of 54.4–281.1 µg/kg) were contaminated with AF levels higher than the proposed limits of the European Union (20 µg/kg). The consumption of canola oil samples used in fried foods had MOE values that were significantly lower as compared to sunflower and soybean oils, indicating that risk reduction is feasible. Additionally, compared to soybean and sunflower oil, canola oil exhibited a greater threat of liver cancer cases linked to AFB1 exposure (17.13 per 100,000 males over 35 and 10.93 per 100,000 females over 35). Using a quantitative liver cancer approach, health risk valuation demonstrated that males and females over the age of 35 are at significant risk of developing liver cancer. The health risk assessment exposed that the males and female over the age of 35 are at considerable risk of liver cancer by using a quantitative liver cancer approach. The innovation of this study lies in the fact that no such study is reported related to liver cancer risk evaluation accompanied with AFB1 exposure from consumed edible oil. As a result, a national strategy must be developed to solve this problem so that edible oil products are subjected to severe regulatory examination

A review on recent advances in covalent organic frameworks-based membranes: Synthesis, modification, and applications in liquid phase separation

The ever-growing global population and the scarcity of clean water resources are major social challenges. In response, researchers are exploring novel materials for water treatment, with a focus on producing high-quality, drinkable water for various uses. Covalent organic frameworks (COFs) are a type of porous organic polymers that possess well-defined pore architectures and are constructed through covalent bonds between organic building blocks. COFs offer considerable potential in the field of membrane separation due to their unique characteristics, such as consistent pore sizes, regular pores, and diverse pore environments. In this review paper, we provide an in-depth evaluation of the recent advancements in the synthesis and modification of COF-based membranes, including the fabrication of hybrid COFs, surface modification, and defect engineering for liquid phase separation. Firstly, we discuss conventional COF processing techniques such as support-assisted, free-standing, and mixed matrix membranes (MMM). Secondly, the reactivity of synthesizing monomers is a critical factor in the development of advanced COF-based membranes. Therefore, we emphasize the nature and reactivity of reacting amine and aldehyde monomers and their significant implications for enhancing the properties and performance of COFs membranes. Finally, we highlight the applications of COF membranes in water treatment, organic solvent nanofiltration, desalination, and heavy metal recovery operations. Our comprehensive review aims to provide an essential guide for researchers in the field of liquid phase separation techniques with an interest in developing unique COF membranes for improved water treatment processes

Preparation and characterization of chitosan/clay composite for direct Rose FRN dye removal from aqueous media: comparison of linear and non-linear regression methods

In the present study, sorption efficacy of chitosan (β-(1→4)-linked d-glucosamine and N-acetyl-d-glucosamine) composite for synthetic direct Rose FRN dye removal from aqueous media was investigated. Chitosan and clay were subjected to chemical modifications to prepare chitosan/clay composite. Batch sorption affecting parameters like pH, composite dose, volume, initial dye concentration, time and temperature were optimized. Maximum sorption capacity (17.18 mg/g) was found within first 40 min of contact. Point of zero charge was found to be 7.0. Linearized and non-linearized regression forms of pseudo 1st and 2nd order kinetic models were used to predict the nature of rate limiting steps involved in the sorption process. Sorption equilibrium data was revealed by applying linear and non-linear equilibrium Langmuir, Freundlich and Redlich–Peterson isotherm models. Calculated values of thermodynamic factors showed that sorption process is exothermic, spontaneous and feasible. Desorption studies were performed for the regeneration of chitosan/clay composite by using different eluting agents. The synthesized composite were characterized by X-ray diffraction (XRD), surface analysis (Brunauer, Emmett and Teller: BET), scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). The developed method was also applied on the real textile effluent for the efficient removal of dyes. Keywords: Chitosan, Composite, Batch sorption, Linear regression, Nonlinear regressio

Environmental remediation and generation of green electricity using constructed wetlands coupled with microbial fuel cell model system

Antibiotic residues in wastewater are considered lethal to the crops and aquatic life. One of the promising way to treat this kind of wastewater is the use of constructed wetlands coupled with microbial fuel cell (CW-MFC). In this treatment, bacterial action and redox operation occurs at anaerobic anode and aerobic cathode respectively. Four different configurations of CW-MFCs was applied for comparison. This study focusses on the investigation of the removal of Co-trimoxazole (CMX), other co-existing pollutants and furthermore, the generation of green electricity with low hydraulic retention time (HRT) was studied. Results revealed that the effluent from configuration 1 (gravel based) had lower (CMX) concentration. This removal performance may be associated to greater electrode absorption capacity for (CMX). The removal efficiency was 92.58% at HRT of 3d and effluent concentration was 4 mg/L. On the other hand, CW-MFC1 exhibited the BOD removal (60.60%) regardless of the increasing effluent antibiotic concentration. Pure strain of Geobactor sulfereducens, adjusted with anaerobic sludge increased the bio-film growth. Maximum power density of 480.2 mW/m−3 observed for CW-MFC1. Electricity generation characteristic were also found to be effected with HRT