Inflammation is the main cause of several autoimmune diseases, including type I diabetes, rheumatoid arthritis, bullous pemphigoid, paraneoplastic pemphigoid, and multiple sclerosis. Currently, there is an urgent demand for the discovery of novel anti-inflammatory drugs with potent activity but also safe for long-term application. Toward this aim, the present study reported the design, synthesis, and characterization of a set of novel 1,3-disubstituted-2-thiohydantoins derivatives. The anti-inflammatory activity of synthesized compounds was assessed against murine leukemia cell line (RAW264.7) by evaluating the cytotoxicity activity and their potency to prevent nitric oxide (NO) production. The results revealed that the synthesized compounds possess a considerable cytotoxic activity together with the ability to reduce the NO production in murine leukemia cell line (RAW264.7). Among synthesized compounds, compound 7 exhibited the most potent cytotoxic activity with IC50 of 197.68 μg/mL, compared to celecoxib drug (IC50 value 251.2 μg/mL), and demonstrated a significant ability to diminish the NO production (six-fold reduction). Exploring the mode of action responsible for the anti-inflammatory activity revealed that compound 7 displays a significant and dose-dependent inhibitory effect on the expression of pro-inflammatory cytokines IL-1β. Furthermore, compound 7 demonstrated the ability to significantly reduce the expression of the inflammatory cytokines IL-6 and TNF-α at 50 μg/mL, as compared to Celecoxib. Finally, detailed molecular modelling studies indicated that compound 7 exhibits a substantial binding affinity toward the binding pocket of the cyclooxygenase 2 enzyme. Taken together, our study reveals that 1,3-disubstituted-2-thiohydantoin could be considered as a promising scaffold for the development of potent anti-inflammatory agents.

Green synthesis of nanoparticles is receiving more attention these days since it is simple to use and prepare, uses fewer harsh chemicals and chemical reactions, and is environmentally benign. A novel strategy aims to recycle poisonous plant chemicals and use them as natural stabilizing capping agents for nanoparticles. In this investigation, silver nanoparticles loaded with latex from Cynanchum acutum L. (Cy-AgNPs) were examined using a transmission electron microscope, FT-IR spectroscopy, and UV-visible spectroscopy. Additionally, using Vicia faba as a model test plant, the genotoxicity and cytotoxicity effects of crude latex and various concentrations of Cy-AgNPs were studied. The majority of the particles were spherical in shape. The highest antioxidant activity using DPPH was illustrated for CAgNPs (25 mg/L) (70.26 ± 1.32%) and decreased with increased concentrations of Cy-AGNPs. Antibacterial activity for all treatments was determined showing that the highest antibacterial activity was for Cy-AgNPs (50 mg/L) with inhibition zone 24 ± 0.014 mm against Bacillus subtilis, 19 ± 0.12 mm against Escherichia coli, and 23 ± 0.015 against Staphylococcus aureus. For phytochemical analysis, the highest levels of secondary metabolites from phenolic content, flavonoids, tannins, and alkaloids, were found in Cy-AgNPs (25 mg/L). Vicia faba treated with Cy-AgNPs- (25 mg/L) displayed the highest mitotic index (MI%) value of 9.08% compared to other Cy-AgNP concentrations (50–100 mg/L) and C. acutum crude latex concentrations (3%). To detect cytotoxicity, a variety of chromosomal abnormalities were used, including micronuclei at interphase, disturbed at metaphase and anaphase, chromosomal stickiness, bridges, and laggards. The concentration of Cy-AgNPs (25 mg/L) had the lowest level of chromosomal aberrations, with a value of 23.41% versus 20.81% for the control. Proteins from seeds treated with V. faba produced sixteen bands on SDS-PAGE, comprising ten monomorphic bands and six polymorphic bands, for a total percentage of polymorphism of 37.5%. Eight ISSR primers were employed to generate a total of 79 bands, 56 of which were polymorphic and 23 of which were common. Primer ISSR 14 has the highest level of polymorphism (92.86%), according to the data. Using biochemical SDS-PAGE and ISSR molecular markers, Cy-AgNPs (25 mg/L) showed the highest percentage of genomic template stability (GTS%), with values of 80% and 51.28%, respectively. The findings of this work suggest employing CyAgNPs (25 mg/L) in pharmaceutical purposes due to its highest content of bioactive compounds and lowest concentration of chromosomal abnormalities.

The combretastatins (cis-stilbenoid molecules) have received significant interest because of their simple chemical structures, excellent antiproliferative activity, and novel anti-tubulin molecular mechanism of action. Significant efforts have been carried out aiming at stabilizing the active cis-isomers. A new series of cis-vinylamide derivatives containing trimethoxyphenyl moiety were synthesized and characterized. Their anticancer activities were evaluated in vitro against MCF-7 breast cancer cell line. Compounds 2f, 3, and 5 displayed potent cytotoxic activity against the breast cancer cell line compared with CA-4 as the reference compound. The microtubule polymerization assay and flow cytometry analysis confirmed that the cytotoxic activity of compound 3 was related to inhibitory activity against tubulin polymerization. Compound 3 showed pro-apoptotic activity by inducting a significant increase in the percentage of pre-G1 phase in DNA flow cytometry compared to untreated control. The pro-apoptotic activity of compound 3 was inferred by a significant increase in the percentage of fluorescent annexin V/PI positive apoptotic cells. It also increased the level of caspase 3 compared to the untreated control.

Background: Hypothyroidism has been linked to many testicular structural and dysfunctional changes in males. Thymoquinone (TQ) has shown a potent testicular protective effect through its antioxidant, anti-inflammatory, antiapoptotic, fertility-enhancing, and endocrine modulatory activities.Objectives: This study aimed to investigate the efficacy of TQ in preserving the testicular structure of a model of experimentally induced hypothyroidism in rats and identify the mechanism behind this effect.Materials and methods: Propylthiouracil (PTU) was used to induce hypothyroidism in adult male Wistar rats, who were then treated with TQ (50 mg/kg/body weight) for 4 weeks and compared to the untreated rats. Thyroid hormonal profile, oxidants/antioxidants profile, and serum testosterone levels were assessed. Gene expression and immune expression of SIRT1 and pro-inflammatory cytokines TNF-α and NF-κB were also assessed in the testicular tissue.Results: TQ administration successfully improved PTU-induced disturbance in the thyroid hormonal profile (T3, T4, and TSH), serum testosterone level, and pancreatic antioxidants compared to the untreated hypothyroid group. TQ significantly downregulated (p = 0.001, p ˂ 0.001) TNF-α and NF-κB transcription, while it significantly upregulated (p = 0.01) SIRT1 transcription in the testes of hypothyroid rats. TQ markedly relieved the histopathological testicular changes induced by PTU and significantly increased (p = 0.002, p = 0.01) the sectional area of seminiferous tubules and germinal epithelial height, respectively. TUNEL-positive apoptotic germinal cells were significantly decreased (p ˂ 0.001), while PCNA-positive proliferating germinal cells and androgen receptor expression were significantly increased (p ˂ 0.001) in the testes of TQ-treated hypothyroid rats.Conclusion: Thymoquinone could limit the hypothyroidism-induced structural changes in the testis, mostly through the upregulation of SIRT1 expression, which seems to mediate its promising antioxidant, anti-inflammatory and antiapoptotic effects that were evident in this study. Therefore, TQ is recommended as an adjuvant safe supplement in managing hypothyroidism, especially in males.

Diabetes mellitus (DM) causes an imbalance in the oxidative status of the human body. Three novel Dapagliflozin (Dapg) Zn (II), Cr (III) and Se (IV) complexes were prepared and characterized by elemental analysis, IR, electronic spectra, magnetic susceptibility, scanning electron microscopy (SEM) and X-ray diffraction. The molar conductance values confirmed the non-electrolytic nature of the Dapg complexes. According to spectral data, Dapg acts as a bidentate ligand. The thermal analyses of the complexes were studied using the DSC technique. The surface morphology and particle sizes of the Dapg complexes were investigated using SEM and XRD. XRD confirmed the crystalline structure for the complexity. This study investigated the effect of novel metal complexes of Dapg with the metals Zn (II), Cr (III) and Se (IV) on oxidative injury and tissue damage in the hepatic tissue of streptozotocin (STZ)-induced diabetic male rats. DM was experimentally induced in male rats. The diabetic rats received Dapg, Dapg/Zn, Dapg/Cr and Dapg/Se orally for 30 successive days. Male rats exposed to STZ showed multi-histopathological alterations in their hepatic tissue, including inflammatory and structural changes. STZ elevated oxidative stress markers in the hepatic tissue and lowered the antioxidant defense enzymes. Supplementation of Dapg with Zn, Cr or Se novel complexes significantly prevented hepatic injury and suppressed the generation of reactive oxygen species. The Dapg/Zn complex was highly effective against Bacillus subtilis and Streptococcus penumonia, while Dapg/Cr was highly effective against Escherichia coli and Pseudomonas aeruginosa, and Dapg/Se was highly effective against Staphylococcus aureas. In conclusion, Dapg novel metal complexes with Zn, Cr or Se protect against oxidative injury and the pathophysiological and bacterial complications of DM and hepatic tissue injury. The Dapg novel metal complexes improved hepatic functions, reduced blood glucose levels and enhanced the levels of antioxidant defense enzymes in diabetic male rats.