N'-(Furan-2-ylmethylene)-2-hydroxybenzohydrazide and its metal complexes: synthesis, spectroscopic investigations, DFT calculations and cytotoxicity profiling.

The ligand, N'-(furan-2-ylmethylene)-2-hydroxybenzohydrazide (H2L), was synthesized characterized through various spectral studies which cleared out that the free ligand existed in keto form. The ligand upon reaction with Cu(II), Co(II), Ni(II) and Zn(II) acetates yielded complexes with stoichiometric ratio 1:2 (M:L) which has been validated through the elemental and mass spectral measurements. The IR and NMR spectral studies of the isolated complexes disclosed that the ligand chelated to metal ion in mononegative bidentate fashion via the azomethine nitrogen and deprotonated enolized carbonyl oxygen. Moreover, the DFT quantum chemical calculations designated that the ligand and Ni(II) complex exhibited the highest and lowest values of HOMO, LUMO energies and HOMO-LUMO energy gap, respectively. Furthermore, the in vitro cytotoxic activity towards HePG-2 and HCT-116 cell lines of the isolated compounds was investigated and the data cleared out that the ligand was more potent than the metal complexes.

Ameliorative Effect of Pomegranate Peel Extract (PPE) on Hepatotoxicity Prompted by Iron Oxide Nanoparticles (Fe2O3-NPs) in Mice.

An evaluation of the ameliorative effect of pomegranate peel extract (PPE) in counteracting the toxicity of iron oxide nanoparticles (Fe2O3-NPs) that cause hepatic tissue damage is focused on herein. Forty male albino mice were haphazardly grouped into four groups as follows: the first control group was orally gavage daily with physiological saline; the second group received 100 mg/kg of PPE by the oral route day after day; the third group received 30 mg/kg Fe2O3-NPs orally; and the fourth group received both PPE and Fe2O3-NPs by the oral route, the same as the second and third sets. Later, after the completion of the experiment, we collected the liver, blood, and bone marrow of bone specimens that were obtained for further laboratory tests. For instance, exposure to Fe2O3-NPs significantly altered serum antioxidant biomarkers by decreasing the levels of total antioxidant capacity (TAC), catalase (CAT), and glutathione s-transferase (GST). Additionally, it caused changes in the morphology of hepatocytes, hepatic sinusoids, and inflammatory Kupffer cells. Furthermore, they significantly elevated the number of chromosomal aberrations including gaps, breaks, deletions, fragments, polyploidies, and ring chromosomes. Moreover, they caused a significant overexpression of TIMP-1, TNF-α, and BAX mRNA levels. Finally, the use of PPE alleviates the toxicity of Fe2O3-NPs that were induced in the hepatic tissues of mice. It is concluded that PPE extract has mitigative roles against the damage induced by Fe2O3-NPs, as it serves as an antioxidant and hepatoprotective agent. The use of PPE as a modulator of Fe2O3-NPs' hepatotoxicity could be considered as a pioneering method in the use of phytochemicals against the toxicity of nanoparticles.

Fast and Reliable Synthesis of Melanin Nanoparticles with Fine-Tuned Metal Adsorption Capacities for Studying Heavy Metal Ions Uptake.

PURPOSE: Adsorption and uptake of heavy metals by polymeric nanoparticles is driven by a variety of physicochemical processes. In this work, we examined heavy metal uptake by synthetic melanin nanoparticles and analyzed physicochemical properties that affect the extent of metal uptake by the nanoparticles. METHODS: Eumelanin nanoparticles were synthesized in a one-pot fast process from a 5,6-diacetoxy indole precursor that is hydrolyzed in situ into dihydroxy indole (DHI). The method allows the possibility of changing the level of sodium ions that ends up in the nanoparticles. Two variants of synthetic DHI-melanin (low-sodium and high sodium variants) were evaluated and demonstrated different relative adsorption efficiencies for heavy metal cations. RESULTS AND DISCUSSION: For the low-sodium DHI-melanin and in terms of percentages of metal ion removal, the relative order of extraction from 50 ppm solutions was Zn2+ > Cd2+ > Ni2+ > Co2+ > Cu2+ > Pb2+, with the extraction percentages ranging from 90% down to 76%, for a 30-minute adsorption time before equilibrium. The lower-sodium DHI-melanin consistently removed more Zn2+ than the higher-sodium variant. Electron microscopy (SEM) showed an increase in melanin particle size after metal ions uptake. In addition, X-ray photoelectron spectroscopy (XPS) of DHI-melanin particles with depth profiling after Zn ions uptake supported particle swelling and ion transport within the particles. CONCLUSION: These initial studies showed the potential of this straightforward synthesis to obtain synthetic DHI-melanin nanoparticles similar to those from biological sources with the possibility to fine-tune their metal adsorption capacity. These synthetic nanoparticles can be used either for the removal of a variety of metal ions or to mimic and study mechanisms of metal uptake by melanin deriving from biological sources, with the potential to understand, for instance, differential heavy metal uptake by various melanic pigments.

Phytochemicals of Rhus spp. as Potential Inhibitors of the SARS-CoV-2 Main Protease: Molecular Docking and Drug-Likeness Study.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China and spread to cover the entire world with an ongoing pandemic. The magnitude of the situation and the fast spread of the new and deadly virus, as well as the lack of specific treatment, led to a focus on research to discover new therapeutic agents. AIM: In this study, we explore the potential inhibitory effects of some active polyphenolic constituents of Rhus spp. (sumac) against the SARS-CoV-2 main protease enzyme (Mpro; 6LU7). METHODS: 26 active polyphenolic compounds of Rhus spp. were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SARS-CoV-2 Mpro. RESULTS: The results show that all tested compounds of sumac provided good interaction with the main active site of SARS-CoV-2 Mpro, with better, lower molecular docking energy (kcal/mol) compared to the well-known drugs chloroquine and favipiravir (Avigan). Only six active polyphenolic compounds of Rhus spp. (sumac), methyl 3,4,5-trihydroxybenzoate, (Z)-1-(2,4-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)-2-hydroxyprop-2-en-1-one, (Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxybenzofuran-3(2H)-one, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-4-one, 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4H-chroman-4-one, and 3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, were proposed by drug likeness, solubility in water, and SAS analysis as potential inhibitors of Mpro that may be used for the treatment of COVID-19. CONCLUSION: Six phenolic compounds of Rhus spp. are proposed for synthesis as potential inhibitors against Mpro and have potential for the treatment of COVID-19. These results encourage further in vitro and in vivo investigations of the proposed ligands and research on the preventive use of Rhus spp. against SARS-CoV-2.

Anti-rheumatic potential of ethyl 2-(2-cyano-3-mercapto-3-(phenylamino) acrylamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate and its Co(II), Cu(II) and Zn(II) complexes.

Ethyl 2-(2-cyano-3-mercapto-3-(phenylamino)acrylamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [THBTD] and its [Co(THBTD]-H)Ac], [Cu(THBTD]-H)Ac]H2O and [Zn(THBTD)-H)Ac] complexes have been synthesized via the reaction of thiocarbamoyl derivatives with metal ions namely; Co(II), Cu(II) and Zn(II) acetate, respectively. The newly synthesized complexes were characterized by elemental analysis, spectral analysis (UV-Vis, IR, (1)H NMR and EPR), conductance, thermal analysis and magnetic moments. The in vivo collagen-adjuvant arthritis model in rats revealed significant antioxidant, analgesic and anti-rheumatic effects for [THBTD] and its copper complex.