PREPARATION, SPECTROSCOPIC, THERMAL AND MOLECULAR DOCKING STUDIES OF COVID-19 PROTEASE ON THE MANGANESE(II), IRON(III), CHROMIUM(III) AND COBALT(II) CREATININE COMPLEXES

Creatinine biomolecule has three different coordination modes through the (exocyclic O(5) and ring N(1)), (imine N(2) and ring N(1)) or as monodentate ligand via exocyclic O(1)). The FTIR and electronic spectra of the synthesized manganese(II), iron(III), chromium(III), and cobalt(II) complexes consistent with the coordinated behavioral derived from the structural analyses. Thermogravimetric data agree with the stoichiometry and proposed formulas [Mn(C4H7N3O)(2)(Cl)(2)](4)H2O, [Fe(C4H7N3O)(2)(Cl)(2)]Cl center dot 6H(2)O, [Cr(C4H7N3O)(2)(Cl)(2)]Cl center dot 6H(2)O, and [Co(C4H7N3O)(2)(Cl)(2)]6H(2)O. Four new transition metal complexes derived from the reaction of creatinine chelate and metal salt (MnCl2 center dot 4H(2)O, FeCl3 center dot 6H(2)O, CrCl3 center dot 6H(2)O, and CoCl2 center dot 6H(2)O), were prepared with 1:2 (metal: ligand) stoichiometry, isolated and well characterized by a different spectral and analytical techniques including FTIR, UV/Vis, magnetic susceptibility, molar conductance, elemental analysis, and TGA/DrTGA/DTA. The solid complexes were formed with the binding of the creatinine ligand through exocyclic O(5) and ring N(1) and presented as an octahedral geometry. In addition molecular docking calculations have been performed between complexes of manganese(II), iron(III), chromium(III) and cobalt(II) with creatinine biomolecule ligand with the Covid-19 protease (6LU7) to determine the best binding site and its inhibitory effect.

Synthesis and spectroscopic interpretations of Co(II), Ni(II) and Cu(II) decxycholate complexes with molecular docking of COVId-19 protease

Co(II), Ni(II) and Cu(II) decxycholate complexes are interesting due to their biologically active and deliberate interest in the research due to their coordination properties. The microanalytical 'elemental analysis', molar conductivity, (infrared and Raman) spectroscopy, thermal analyses (TGA/DSC), UV-vis spectra, and ESR for copper(II) decxycholate complex investigations were performed in the structural assignments of Co(II), Ni(II) and Cu(II) decxycholate complexes. Reaction of the sodium deoxycholate ligand (C24H39O4Na) with three transition metal ions form the complexes of formulae, [M(C24H39O4)(2)(H2O)(2)] center dot xH(2)O where M = Co(II), Ni(II) and Cu(II) where x = 2 for Cu(II) and x = 4 in case of M = Co(II) or Ni(II) metal ions. The FTIR spectra of the complexes show that decxycholate molecule is present as bidentate ligand. Molecular docking utilizing to additionally examine the interaction of COVID-19 (6LU7) with different complexes of deoxycholic acid with Co(II), Ni(II) and Cu(II). Furthermore, in the case of Co(II) deoxycholate complex, the probe is surrounded by amino residues Met235, Pro241, Glu240, Pro108, Gln110, Phe294, and Ile152. The probe molecule of Ni(II) deoxycholate complex is sited close to amino acids Tyr126, Tyr239, Leu287, Leu272, and Lys137. For, Cu(II) deoxycholate complex, the residues of amino acids comprise of Pro132, Pro108, Gln110, Gly109, Ile200, Asn203, Val202, His246, Pro293 and Tyr154. The binding energy was determined from the docking reads for Co(II)-6LU7, Ni(II)-6LU7 and Cu(II)-6LU7 deoxycholate compounds were found to be -446.99, -500.52, -398.13 kcal mol-1 individually.

New Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II), and Hg(II) Gibberellate Complexes: Synthesis, Structure, and Inhibitory Activity Against COVID-19 Protease.

Transition metals such as Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II), and Hg(II) have been reacted with gibberellic acid (HGA) to give novel complexes, and those have been characterized by physical, spectral and analytical methods. The plant hormone gibberellate acts as a deprotonated bidentate ligand in the complexation reaction with central metal ions in the ratio 1 : 2 (M n+ : GA). The complexes [M(GA)2(H2O)2], where [M = Mn(II), Co(II), and Ni(II)] form octahedral structures, while [M(GA)2] complexes [M = Zn(II), Cd(II), and Hg(II)] display four-coordination geometry. The octahedral structures of Cr(III) and Fe(III) complexes are characterized by the general formula [M(GA)2(H2O)(Cl)]. Computational study carried out has determined possible interactions of the complexes with COVID-19 (6LU7).

Antioxidant, antigenotoxic, and hepatic ameliorative effects of quercetin/zinc complex on cadmium-induced hepatotoxicity and alterations in hepatic tissue structure

Applications of medicinal uses of metals and their complexes have been gaining major clinical significance, especially during the COVID-19 pandemic. The ligation behavior of quercetin (Q), a flavonoid, and Zn metal, i.e., the Zn/Q complex, was fully characterized based on molar conductance, infrared (IR) spectra, elemental analysis, electronic spectra, thermogravimetric analysis, proton nuclear magnetic resonance (1H-NMR), and transmission electron microscopy (TEM) in our lab. Hepatotoxicity was induced by cadmium (CdCl2 ). A total of 40 male albino rats were randomly distributed into the following four groups: Control, hepatotoxic group (CdCl2 ), Zn/Q-treated group, and group treated with a combination of CdCl2 and Zn/Q. Serum hepatic enzymes (AST, ALT, and LDH), total protein, and enzymatic and nonenzymatic antioxidant levels were determined. Histology and TEM for hepatic tissues, in addition to the gene expression of SOD as an antioxidant enzyme in the hepatic tissues, were evaluated. The Q/Zn treatment demonstrated potent protective effects against CdCl2-induced sever oxidative stress and suppressed hepatic toxicity, genotoxicity, liver enzyme disturbances, and structural alterations. In conclusion, the Zn/Q complex produced a high potent antioxidant effect against the oxidative injury and genotoxicity induced by CdCl2 and could be considered to be a potent ameliorative hepatoprotective agent against CdCl2 hepatotoxicity, which could be beneficial during the COVID-19 pandemic. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Synthesis of N,N'-bis(1,5-dimethyl-2-phenyl-1,2-dihydro-3-oxopyrazol-4-yl) sebacamide that ameliorate osteoarthritis symptoms and improve bone marrow matrix structure and cartilage alterations induced by monoiodoacetate in the rat model: "Suggested potent anti-inflammatory agent against COVID-19".

To assess the chondroprotective effect and influence of N,N'-bis(1,5-dimethyl-2-phenyl-1,2-dihydro-3-oxopyrazol-4-yl) sebacamide (dpdo) that was synthesized through the reaction of phenazone with sebacoyl chloride and screened for its biological activity especially as anti-arthritic and anti-inflammatory agent in a monoiodoacetate (MA)-induced experimental osteoarthritis (OA) model. Thirty male albino rats weighing "190-200 g" were divided randomly into three groups (10 each): control, MA-induced OA, and MA-induced OA + dpdo. In MA-induced OA rat, the tumor necrosis factor alpha, interleukin 6, C-reactive protein, rheumatoid factors, reactive oxygen species, as well as all the mitochondrial markers such as mitochondria membrane potential, swelling mitochondria, cytochrome c oxidase (complex IV), and serum oxidative/antioxidant status (malondialdehyde level and activities of myeloperoxidase and xanthine oxidase) are elevated. Also, the activity of succinate dehydrogenase (complex II), levels of ATP, the level of glutathione (GSH), and thiol were markedly diminished in the MA-induced OA group compared to the normal control rats. These findings showed that mitochondrial function is associated with OA pathophysiological alterations and high gene expressions of (IL-6, TNF-a, and IL-1b) and suggests a promising use of dpdo as potential ameliorative agents in the animal model of OA and could act as anti-inflammatory agent in case of severe infection with COVID-19. It is clearly appeared in improving the bone cortex and bone marrow in the treated group with the novel compound in histological and transmission electron microscopic sections which is a very important issue today in fighting severe infections that have significant effects on the blood indices and declining of blood corpuscles like COVID-19, in addition to declining the genotoxicity and inflammation induced by MA in male rats. The novel synthesized compound was highly effective in improving all the above mentioned parameters.

Assessment of hepatoprotective, renal protective and anti-genotoxic effect of novel synthesized complexes of Ca(II), Mg(II) and Cr(III) with 2,6-dichloroindophenol against Acrylamide toxicity in male rats

Herein this study aimed to prepare and spectroscopically investigate magnesium(II), calcium(II) and chromium(III) complexes with 2,6-dichloroindo phenol sodium hydrate (Dich). The suggestion formula can be presented as [Mg(Dich)2(H2O)4].5H2O, [Ca(Dich)2(H2O)4].2H2O and [Cr(Dich)3(H2O)3].3H2O according to micro analytical, conductivity, FTIR, magnetic susceptibility, UV-Visible, TG-DrTGA, SEM and TEM studies. The analyses revealed that the Dich ligand acts as a monodentate chelating through the oxygen atom of-OH phenolic group with an octahedral geometry around the central metal ions. The six-coordination sphere was completing by coordinated water molecules. This study aimed to evaluate the potent antioxidant, antihepatorenal toxicity and antigenotoxic effects of acrylamide (AC) and role of the novel complexes Ca/Dich, Mg/Dich and Cr/Dich in alleviating hepatorenaltoxicity, oxidative injury and genotoxicity induced by AC in male albino rats. After 30 consecutive days of exposure, some biochemical parameters were measured as hepatic aminotransferases enzymes, lipid profile, kidney function parameters, TNF-α, IL-6, markers of inflammation, tissue damage LDH, CRP, mitochondrial potential activities, MPO, XO, CRP,SDH , MMP , MDA levels and antioxidant enzymes (SOD , CAT , GRx and GST) ,ATP content with histological, TEM examination of the hepatic and renal tissues and Alkaline comet assay in hepatic tissues . AC induced biochemical and cellular alterations in the hepatic and renal tissues and theses toxicity were alleviated greatly after treatment of male rats with the novel complexes Ca/Dich, Mg/Dich and Cr/Dich which afforded protection against hepatorenal injury and oxidative stress resulting from AC toxicity. Consequently, the novel complexes improved thehepatic enzymes and improved the antioxidant capacities in the hepatic and renal tissues. © 2021 World Research Association. All rights reserved.