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

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

Evaluation and detoxification of aflatoxins in ground and tree nuts using food grade organic acids

The contamination of foodstuffs especially nuts with aflatoxins (AFs) affected by some of the fungal genera species is a major threat to the economy, safe food supply and serious health concerns to any country in recent days. Recently different techniques including heat, ozone and microbes are used for the decontamination of aflatoxin but all these are limited to achieve the desirable results. The present study objectives to decontaminate AFs in nuts by using three food-grade organic acids. The aqueous solutions of three food-grade organic acids namely citric, lactic and propionic acid are used at five different concentrations (1, 3, 5, 7 and 9%) to detoxify aflatoxin B1 (AFB1) and total aflatoxins (TAFs) that includes ;AFB1, AFB2, AFG1 and AFG2 in selected nuts including almond, peanut, pistachio and walnut at two different moisture levels (10 ± 3 and 16 ± 3%). The high-performance liquid chromatography (HPLC) coupled with fluorescence detection method was applied for the qualitative and quantitative determination of AFs. The results showed that the decontamination of AFB1 and TAFs significantly increased in infected nuts by increasing the concentration of acids. The experimental results after 15 min treatment of walnut (10 ± 3 and 16 ± 3% moisture level), pistachio (10 ± 3% moisture content) and peanuts (10 ± 3% moisture content) with citric, lactic and propionic acids at 9% concentration significantly reduced AFs about 99, 99.90 and 96.07% respectively. Furthermore, treatment with citric and lactic acids resulted in the conversion of AFB1 into less toxic products identified as AFD1 via hydrolysis of the lactone ring. Furthermore, citric acid was found as the most efficient acid in degrading the TAFs among all three organic acids. The present study showed better AFs detoxification results than conventional methods. Hence, it is concluded that citric, lactic, and propionic acids can be applied as a useful and safe decontamination method for AFB1 and TAFs in aflatoxin-affected nuts

Starch and polyvinyl alcohol encapsulated biodegradable nanocomposites for environment friendly slow release of urea fertilizer

Low nitrogen (N) use efficiency from urea fertilizers due to environmental losses results in high cost of fertilizers for agricultural productions. Coating of urea with biodegradable polymers makes them effective for control and efficient N release. In this study, starch and polyvinyl alcohol (PVA) were used in combination with acrylic acid (AA), citric acid (CA) and maleic acid (MA) for the coating of urea prills. Different formulations of the coating were prepared and applied on urea prills such as urea coated with starch (10%) and PVA (5%) with acrylic acid: 2, 4 and 6% (USP-A2, USP-A4, USP-A6), with citric acid: 2, 4 and 6% (USP-C2, USP-C4, USP-C6), and with maleic acid: 2, 4 and 6% (USP-M2, USP-M4, USP-M6). After urea coating in fluidized bed coater, all uncoated and coated urea samples were characterized by scanning electron spectroscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), crushing strength and UV-Vis spectroscopy. The morphological and XRD analysis indicated that a new uniform coating with no new phase transformation occurred. Among all urea coated samples, USP-A2 and USP-C2 showed the highest crushing strengths: 12.08 and 13.67 N with nitrogen release efficiency of 70.10 and 50.74% respectively. All coated urea samples improved the spinach plants’ foliage yield, chlorophyll content, N-uptake and apparent nitrogen recovery (ANR) than uncoated urea and control plants. However, USP-A2 and USP-C2 provided promising results among all coated samples with dry foliage yield (2208 ± 92 and 2428 ± 83 kg/ha), chlorophyll (34 ± 0.6 and 34 ± 0.4 mg/g), N-uptake (88 ± 4 and 95 ± 6 kg/ha) and ANR (59 ± 4 and 67 ± 6%). Therefore, urea prills coated with a combination of biodegradable polymers can be a better choice for the farmers to enhance agronomical productions by controlling the fertilizer nutrient release rate

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

Role of ulema in modern Kashmir.

The present work is divided into four chapters. The first chapter has been brought out the fact that many of the ulema of the period of study owned their ancestry to the ulema families that existed in Kashmir right from the establishment of the Muslim ruler .The second chapter is an effort to study the social background of the ulema for the period under view. The 3rd chapter analyses the contribution of the ulema to the society, culture, politics and economy in the valley. The 4th chapter deals with the role of the ulema in respect of the mass awakening against administrative highhandedness, social injustice and economic imbalances in vogue during the reign of the Dogra's in Kashmir

Microbial fuel cells a state-of-the-art technology for wastewater treatment and bioelectricity generation

Wastewater treatment and electricity generation have been the major concerns for the last few years. The scarcity of fossil fuels has led to the development of unconventional energy resources that are pollution-free. Microbial fuel cell (MFC) is an environmental and eco-friendly technology that harvests energy through the oxidation of organic substrates and transform into the electric current with the aid of microorganisms as catalysts. This review presents power output and colour removal values by designing various configurations of MFCs and highlights the importance of materials for the fabrication of anode and cathode electrodes playing vital roles in the formation of biofilm and redox reactions taking place in both chambers. The electron transfer mechanism from microbes towards the electrode surface and the generation of electric current are also highlighted. The effect of various parameters affecting the cell performance such as type and amount of substrate, pH and temperature maintained within the chambers have also been discussed. Although this technology presents many advantages, it still needs to be used in combination with other processes to enhance power output

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