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

Radioiodine-131 Therapy Used for Differentiated Thyroid Cancer Can Impair Titanium Dental Implants: An In Vitro Analysis

Background: The aim was to assess, in vitro, the effects of radioiodine-131 (I-131) on the structure of titanium implants. Material and Methods: A total of 28 titanium implants were divided into 7 groups (n = 4) and irradiated at 0, 6, 12, 24, 48, 192 and 384 hours. At the end of the experiment, each sample was investigated via scanning electron microscopy (SEM) and electrochemical measures. Results: The control sample revealed a smooth and compact surface. The small micro-sized porosity is slightly visible at the macroscopic level, but the precise details cannot be observed. A mild exposure to the radioactive solution for 6 to 24 h showed a good preservation of the macro-structural aspects such as thread details and surface quality. Significant changes occurred after 48 h of exposure. It was noticed that the open-circuit potential (OCP) value of the non-irradiated implants move toward more noble potentials during the first 40 min of exposure to the artificial saliva and then stabilizes at a constant value of −143 mV. A displacement of the OCP values toward more negative values was observed for all irradiated implants; these potential shifts are decreasing, as the irradiation period of the tested implants increased. Conclusion: After exposure to I-131, the structure of titanium implants is well preserved up to 12 h. The eroded particles start to appear in the microstructural details after 24 h of exposure and their numbers progressively increase up to 384 h after exposure

The Side Effects of Therapeutic Radioiodine-131 on the Structure of Enamel and Dentin in Permanent Human Teeth

Radioiodine-131 (I-131) is an essential therapy for patients with differentiated thyroid carcinomas (DTC). Generally, I-131 is safe and well tolerated, but patients may present early or late complications in the oral and maxillofacial areas. Thus, the aim of this study was to evaluate in-vitro, the alteration of enamel and dentin after I-131 exposure using histopathological assessment, scanning electron microscopy (SEM) and atomic force microscopy (AFM). For I-131 irradiation, an in-vitro protocol was used that simulates the procedure for irradiation therapy performed for patients with DTCs. A total of 42 teeth were divided into seven groups (n = 6) and irradiated as follows: control, irradiation groups (3, 6, 12, 36, 48 h, 8 days). Histological changes were observed at 48 h (enamel surface with multifocal and irregular areas) and at 8 days (enamel surface with multiple, very deep, delimited cavities). SEM imaging revealed the enamel destruction progresses along with the treatment time increasing. The alterations are extended into the enamel depth and the dislocated hydroxyapatite debris is overwhelming. The enamel-dentine interface shows small gaps after 6 h and a very well developed valley after 12 h; the interface microstructure resulted after 8 days is deeply altered. The AFM imaging shows that I-131 affects the protein bond between hydroxyapatite nano-crystals causing loss of cohesion, which leads to significant increasing of nano-particles diameter after 6 h. In conclusion, both enamel and dentin appear to be altered between 12 and 48 h and after 8 days of treatment are extended in depth