The burden of persistent symptoms after COVID-19 (long COVID): a meta-analysis of controlled studies in children and adults.

BACKGROUND: Previous meta-analyses estimating the prevalence of the post-COVID-19 condition (PCC) were confounded by the lack of negative control groups. This may result in an overestimation of the prevalence of those experiencing PCC, as these symptoms are non-specific and common in the general population. In this study, we aimed to compare the burden of persistent symptoms among COVID-19 survivors relative to COVID-19-negative controls. METHODS: A systematic literature search was conducted using the following databases (PubMed, Web of Science, and Scopus) until July 2023 for comparative studies that examined the prevalence of persistent symptoms in COVID-19 survivors. Given that many of the symptoms among COVID-19 survivors overlap with post-hospitalization syndrome and post-intensive care syndrome, we included studies that compare the prevalence of persistent symptoms in hospitalized COVID-19 patients relative to non-COVID-19 hospitalized patients and in non-hospitalized COVID-19 patients relative to healthy controls that reported outcomes after at least 3 months since infection. The results of the meta-analysis were reported as odds ratios with a 95% confidence interval based on the random effects model. RESULTS: Twenty articles were included in this study. Our analysis of symptomatology in non-hospitalized COVID-19 patients compared to negative controls revealed that the majority of symptoms examined were not related to COVID-19 infection and appeared equally prevalent in both cohorts. However, non-COVID-19 hospitalized patients had higher odds of occurrence of certain symptoms like anosmia, ageusia, fatigue, dyspnea, and brain fog (P < 0.05). Particularly, anosmia and ageusia showed substantially elevated odds relative to the negative control group at 11.27 and 9.76, respectively, P < 0.05. In contrast, analysis of hospitalized COVID-19 patients compared to those hospitalized for other indications did not demonstrate significantly higher odds for the tested symptoms. CONCLUSIONS: The persistent symptoms in COVID-19 survivors may result from hospitalization for causes unrelated to COVID-19 and are commonly reported among the general population. Although certain symptoms exhibited higher odds in non-hospitalized COVID-19 patients relative to controls, these symptoms are common post-viral illnesses. Therefore, the persistent symptoms after COVID-19 may not be unique to SARS-CoV-2. Future studies including well-matched control groups when investigating persistent symptoms in COVID-19 survivors are warranted to draw a firm conclusion.

Potential Anticancer Activity of Juniperus procera and Molecular Docking Models of Active Proteins in Cancer Cells.

Medicinal plants provide a wide range of active compounds that can be exploited to create novel medicines with minimal side effects. The current study aimed to identify the anticancer properties of Juniperus procera (J. procera) leaves. Here, we demonstrate that J. procera leaves' methanolic extract suppresses cancer cells in colon (HCT116), liver (HepG2), breast (MCF-7), and erythroid (JK-1) cell lines. By applying GC/MS, we were able to determine the components of the J. procera extract that might contribute to cytotoxicity. Molecular docking modules were created that used active components against cyclin-dependent kinase 5 (Cdk5) in colon cancer, aromatase cytochrome P450 in the breast cancer receptor protein, the -N terminal domain in the erythroid cancer receptor of the erythroid spectrin, and topoisomerase in liver cancer. The results demonstrate that, out of the 12 bioactive compounds generated by GC/MS analysis, the active ingredient 2-imino-6-nitro-2H-1-benzopyran-3-carbothiamide proved to be the best-docked chemical with the chosen proteins impacted by DNA conformational changes, cell membrane integrity, and proliferation in molecular docking studies. Notably, we uncovered the capacity of J. procera to induce apoptosis and inhibit cell growth in the HCT116 cell line. Collectively, our data propose that J. procera leaves' methanolic extract has an anticancer role with the potential to guide future mechanistic studies.

Synthesis and Characterization of an α-Fe2O3-Decorated g-C3N4 Heterostructure for the Photocatalytic Removal of MO.

This study describes the preparation of graphitic carbon nitride (g-C3N4), hematite (α-Fe2O3), and their g-C3N4/α-Fe2O3 heterostructure for the photocatalytic removal of methyl orange (MO) under visible light illumination. The facile hydrothermal approach was utilized for the preparation of the nanomaterials. Powder X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray (EDX), and Brunauer-Emmett-Teller (BET) were carried out to study the physiochemical and optoelectronic properties of all the synthesized photocatalysts. Based on the X-ray photoelectron spectroscopy (XPS) and UV-visible diffuse reflectance (DRS) results, an energy level diagram vs. SHE was established. The acquired results indicated that the nanocomposite exhibited a type-II heterojunction and degraded the MO dye by 97%. The degradation ability of the nanocomposite was higher than that of pristine g-C3N4 (41%) and α-Fe2O3 (30%) photocatalysts under 300 min of light irradiation. The formation of a type-II heterostructure with desirable band alignment and band edge positions for efficient interfacial charge carrier separation along with a larger specific surface area was collectively responsible for the higher photocatalytic efficiency of the g-C3N4/α-Fe2O3 nanocomposite. The mechanism of the nanocomposite was also studied through results obtained from UV-vis and XPS analyses. A reactive species trapping experiment confirmed the involvement of the superoxide radical anion (O2•-) as the key reactive oxygen species for MO removal. The degradation kinetics were also monitored, and the reaction was observed to be pseudo-first order. Moreover, the sustainability of the photocatalyst was also investigated.

QSAR Modeling, Molecular Docking and Cytotoxic Evaluation for Novel Oxidovanadium(IV) Complexes as Colon Anticancer Agents.

Four new drug-based oxidovanadium (IV) complexes were synthesized and characterized by various spectral techniques, including molar conductance, magnetic measurements, and thermogravimetric analysis. Moreover, optimal structures geometry for all syntheses was obtained by the Gaussian09 program via the DFT/B3LYP method and showed that all of the metal complexes adopted a square-pyramidal structure. The essential parameters, electrophilicity (ω) value and expression for the maximum charge that an electrophile molecule may accept (ΔNmax) showed the practical biological potency of [VO(CTZ)2] 2H2O. The complexes were also evaluated for their propensity to bind to DNA through UV-vis absorption titration. The result revealed a high binding ability of the [VO(CTZ)2] 2H2O complex with Kb = 1.40 × 106 M-1. Furthermore, molecular docking was carried out to study the behavior of the VO (II) complexes towards colon cancer cell (3IG7) protein. A quantitative structure-activity relationship (QSAR) study was also implemented for the newly synthesized compounds. The results of validation indicate that the generated QSAR model possessed a high predictive power (R2 = 0.97). Within the investigated series, the [VO(CTZ)2] 2H2O complex showed the greatest potential the most selective compound comparing to the stander chemotherapy drug.

Theoretical Investigation by DFT and Molecular Docking of Synthesized Oxidovanadium(IV)-Based Imidazole Drug Complexes as Promising Anticancer Agents.

Vanadium compounds have been set in various fields as anticancer, anti-diabetic, anti-parasitic, anti-viral, and anti-bacterial agents. This study reports the synthesis and structural characterization of oxidovanadium(IV)-based imidazole drug complexes by the elemental analyzer, molar conductance, magnetic moment, spectroscopic techniques, as well as thermal analysis. The obtained geometries were studied theoretically using density functional theory (DFT) under the B3LYP level. The DNA-binding nature of the ligands and their synthesized complexes has been studied by the electronic absorption titrations method. The biological studies were carried with in-vivo assays and the molecular docking method. The EPR spectra asserted the geometry around the vanadium center to be a square pyramid for metal complexes. The geometries have been confirmed using DFT under the B3LYP level. Moreover, the quantum parameters proposed promising bioactivity of the oxidovanadium(IV) complexes. The results of the DNA-binding revealed that the investigated complexes bind to DNA via non-covalent mode, and the intrinsic binding constant (Kb) value for the [VO(SO4)(MNZ)2] H2O complex was promising, which was 2.0 × 106 M-1. Additionally, the cytotoxic activity of the synthesized complexes exhibited good inhibition toward both hepatocellular carcinoma (HepG-2) and human breast cancer (HCF-7) cell lines. The results of molecular docking displayed good correlations with experimental cytotoxicity findings. Therefore, these findings suggest that our synthesized complexes can be introduced as effective anticancer agents.

Oxazinethione Derivatives as a Precursor to Pyrazolone and Pyrimidine Derivatives: Synthesis, Biological Activities, Molecular Modeling, ADME, and Molecular Dynamics Studies.

In this study, we used oxazinethione as a perfect precursor to synthesize new pyrimidine and pyrazole derivatives with potent biological activities. Biological activities were determined for all compounds against A. flavus, E. coli, S. aureus, and F. moniliform. Compounds 3, 4a-b, and 5 exhibited higher activities toward A. flavus, E. coli, S. aureus, and F. moniliform; this was indicated through the MIC (minimum inhibitory concentration). At the same time, anticancer activities were determined through four cell lines, Ovcar-3, Hela, MCF-7, and LCC-MMk. The results obtained indicated that compound 5 was the most potent compound for both cell lines. Molecular docking was studied by the MOE (molecular operating environment). The in silico ADME of compounds 2 and 5 showed good pharmacokinetic properties. The present research strengthens the applicability of these compounds as encouraging anticancer and antibacterial drugs. Moreover, JAGUAR module MD simulations were carried out at about 100 ns. In addition, spectroscopic studies were carried out to establish the reactions of the synthesized structure derivatives.

Computational Approaches for the Design of Novel Anticancer Compounds Based on Pyrazolo[3,4-d]pyrimidine Derivatives as TRAP1 Inhibitor.

In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R2 = 0.96 and Q2 = 0.57. Leave one out (LOO) cross-validation (R2 CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (-11.265, -10.532, -10.422, -10.827, -10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors.

DNA-Binding and Anticancer Activity of Binuclear Gold(I) Alkynyl Complexes with a Phenanthrenyl Bridging Ligand.

3,6-Diethynyl-9,10-diethoxyphenanthrene (4) was synthesized from phenanthrene and employed in the synthesis of the binuclear gold(I) alkynyl complexes (R3P)Au(C≡C-3-[C14H6-9,10-diethoxy]-6-C≡C)Au(PR3) (R = Ph (5a), Cy (5b)). The diyne 4 and complexes 5a and 5b were characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. UV-Vis spectroscopy studies of the metal complexes and precursor diyne show strong p à p* transitions in the near UV region that red shift by ca. 50 nm upon coordination at the gold centers. The emission spectrum of 4 shows an intense fluorescence band centered at 420 nm which red shifts, slightly upon coordination of 4 to gold. Binding studies of 4, 5a, and 5b against calf thymus DNA were carried out, revealing that 4, 5a, and 5b have >40% stronger binding affinities than the commonly used intercalating agent ethidium bromide. The molecular docking scores of 4, 5a, and 5b with B-DNA suggest a similar trend in behavior to that observed in the DNA-binding study. Unlike the ligand 4, promising anticancer properties for 5a and 5b were observed against several cell lines; the DNA binding capability of the precursor alkyne was maintained, and its anticancer efficacy enhanced by the gold centers. Such phenanthrenyl complexes could be promising candidates in certain biological applications because the two components (phenanthrenyl bridge and metal centers) can be altered independently to improve the targeting of the complex, as well as the biological and physicochemical properties.

DNA-Binding Capabilities and Anticancer Activities of Ruthenium(II) Cymene Complexes with (Poly)cyclic Aromatic Diamine Ligands.

Ruthenium(II) arene complexes of the general formula [RuCl(η6-p-cymene)(diamine)]PF6 (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru-Nguanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC50) values comparable to or better than cisplatin against three cell lines.

Fibro-check: a combination of direct and indirect markers for liver fibrosis staging in chronic hepatitis C patients.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decision. This study was concerned with determining the levels of collagen III and its degrading enzyme matrix metalloproteinase-1 (MMP-1) as direct and complementary markers for liver fibrosis staging. RESULTS: A total of 269 chronic hepatitis C patients constituted this study. Western blotting was used for identifying collagen III and MMP-1 in serum samples. As a result, collagen III and MMP-1 were identified, respectively, at 70 and 245 kDa using their respective mono-specific antibodies. These two markers were quantified in sera of patients using ELISA. Next, Fibro-check was constructed combining collagen III and MMP-1 together with other indirect markers which reflect alteration in hepatic functions that proved useful to stage liver fibrosis. Fibro-check produced area under the receiver-operating characteristic curve (AUC) 0.91 and 0.83 for significant (F2-F4) and cirrhosis (F4), respectively. Additionally, we estimated the performance of Fibro-check in comparison with aspartate to platelet ratio index (APRI) and fibrosis index. Fibro-check seems to be more efficient than both of them. Fibro-check was then applied to the validation study to test its accuracy and reproducibility showing AUCs 0.90 for F2-F4 and 0.86 for F4. CONCLUSIONS: Fibro-check combining 'direct' and 'indirect' markers using a mathematical formula may improve the staging of liver fibrosis with a high degree of accuracy and seems more efficient than APRI and Fibrosis index in this group of Egyptian patients.

Exploring novel NH-form resorcinol-based schiff base and its metal complexes: Synthesis, characterization, cytotoxic activity, molecular docking and ADME studies.

The research investigates the cytotoxic effects of the stable NH-form of a resorcinol-based Schiff base (HL) and its metal complexes (Zn(II), Cd(II), Cu(II), Ni(II)) on MCF-7 breast cancer cells. The structural characterization was conducted utilizing diverse analytical techniques, including mass spectrometry, elemental analysis, molar conductance, magnetic moment, UV-Vis, IR and ESR. The crystalline state analysis of HL through X-ray crystallography disclosed a hybrid structure comprising two canonical forms, specifically the quinoid and zwitterion, that contribute to resonance and diverse interactions, resulting in the development of a three-dimensional form. NMR, IR and ESR analyses showed that the HL was bidentate, using the oxygen of the hydroxyl and the nitrogen atom of azomethine, bonded to the metal center during complexation. The study explored the cytotoxic effects of HL and the various metal complexes on MCF-7 human breast cancer cells. All complexes display significant cytotoxicity (IC50 < 38.37 µM). The activity of the complexes was greater than that of the free ligand, with the Cu(II) complex followed by Zn(II) demonstrated superior cytotoxicity compared to Cd(II), and Ni(II) complexes. Notably, the Cu(II) and Zn(II) complex exhibited approximately 13.2 and 12.9 times greater cytotoxicity than the 5-F Uracil (5-FU) cancer drug. An MTT assay corroborated the antiproliferative activity. The molecular docking study has been performed for all compounds with the aromatase cytochrome P450 receptor protein associated with breast cancer (PDB code = 3eqm). ADME drug likeness model has been done.

Favorable Heteroaromatic Thiazole-Based Polyurea Derivatives as Interesting Biologically Active Products.

This research sought to synthesize a new set of heteroaromatic thiazole-based polyurea derivatives with sulfur links in the polymers' main chains, which were denoted by the acronyms PU1-5. Using pyridine as a solvent, a diphenylsulfide-based aminothiazole monomer (M2) was polymerized via solution polycondensation with varied aromatic, aliphatic, and cyclic diisocyanates. Typical characterization methods were used to confirm the structures of the premonomer, monomer, and fully generated polymers. The XRD results revealed that aromatic-based polymers had higher crystallinity than aliphatic and cyclic derivatives. SEM was used to visualize the surfaces of PU1, PU4, and PU5, revealing spongy and porous shapes, shapes resembling wooden planks and sticks, and shapes resembling coral reefs with floral shapes at various magnifications. The polymers demonstrated thermal stability. The numerical results for PDTmax are listed in the following order, ranked from lowest to highest: PU1 < PU2 < PU3 < PU5 < PU4. The FDT values for the aliphatic-based derivatives (PU4 and PU5) were lower than those for the aromatic-based ones (616, 655, and 665 °C). PU3 showed the greatest inhibitory impact against the bacteria and fungi under investigation. In addition, PU4 and PU5 demonstrated antifungal activities that, in contrast with the other products, were on the lower end of the spectrum. Furthermore, the intended polymers were also tested for the presence of the proteins 1KNZ, 1JIJ, and 1IYL, which are frequently utilized as model organisms for E. coli (Gram-negative bacteria), S. aureus (Gram-positive bacteria), and C. albicans (fungal pathogens). This study's findings are consistent with the outcomes of the subjective screening.

Olmesartan medoxomil self-microemulsifying drug delivery system reverses apoptosis and improves cell adhesion in trinitrobenzene sulfonic acid-induced colitis in rats.

Olmesartan medoxomil (OM) is an angiotensin receptor blocker. This study aimed to investigate the effects of OM self-microemulsifying drug delivery system (OMS) in trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats. Besides two control groups, five TNBS-colitic-treated groups (n = 8) were given orally sulfasalazine (100 mg/kg/day), low and high doses of OM (3.0 and 10.0 mg/kg/day) (OML and OMH) and of OMS (OMSL and OMSH) for seven days. A colitis activity score was calculated. The colon was examined macroscopically. Colonic levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, and reduced glutathione were measured. Plasma and colonic olmesartan levels were measured. Colonic sections were subjected to hematoxylin and eosin staining and immunohistochemical staining for E-cadherin, caspase-3, and matrix metalloproteinase-9 (MMP-9). Protein expression of E-cadherin, Bcl-2 associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 by Western blot was done. TNBS-colitic rats showed increased colonic myeloperoxidase, TNF-α, IL-6, and malondialdehyde, decreased colonic glutathione, histopathological, immunohistochemical, and protein expression alterations. OMS, compared with OM, dose-dependently achieved higher colonic free olmesartan concentration, showed better anti-inflammatory, antioxidant, and anti-apoptotic effects, improved intestinal barrier, and decreased mucolytic activity. OMS more effectively up-regulated the reduced Bcl-2, Bcl-2/Bax ratio, and E-cadherin expression, and down-regulated the overexpressed Bax, cleaved caspase-3, and MMP-9. OMSL exerted effects comparable to OMH. Sulfasalazine exerted maximal colonic protective effects and almost completely reversed colonic damage, and OMSH showed nearly similar effects with non-significant differences in-between or compared with the normal control group. In conclusion, OMS could be a potential additive treatment for Crohn's disease colitis.

Interactions of selected cardiovascular active natural compounds with CXCR4 and CXCR7 receptors: a molecular docking, molecular dynamics, and pharmacokinetic/toxicity prediction study.

BACKGROUND: The chemokine CXCL12 and its two receptors (CXCR4 and CXCR7) are involved in inflammation and hematopoietic cell trafficking. This study was designed to investigate molecular docking interactions of four popular cardiovascular-active natural compounds; curcumin, resveratrol, quercetin, and eucalyptol; with these receptors and to predict their drug-like properties. We hypothesize that these compounds can modify CXCL12/CXCR4/CXCR7 pathway offering benefits for coronary artery disease patients. METHODS: Docking analyses were carried and characterized by Molecular Environment (MOE) software. Protein Data Bank ( http://www.rcsb.org/ ) has been retrieved from protein structure generation and crystal structures of CXCR4 and CXCR7 receptors (PDB code = 3ODU and 6K3F). The active sites of these receptors were evaluated and extracted from full protein and molecular docking protocol was done for compounds against them. The presented parameters included docking scores, ligand binding efficiency, and hydrogen bonding. The pharmacokinetic/toxic properties (ADME/T) were calculated using SwissADME, ProTox-II, and Pred-hERG softwares to predict drug-like properties of the compounds. The thermochemical and molecular orbital analysis, and molecular dynamics simulations were also done. RESULTS: All compounds showed efficient interactions with the CXCR4 and CXCR7 receptors. The docking scores toward proteins 3ODU of CXCR4 and 6K3F of CXCR7 were - 7.71 and - 7.17 for curcumin, - 5.97 and - 6.03 for quercetin, - 5.68 and - 5.49 for trans-resveratrol, and - 4.88 and - 4.70 for (1 s,4 s)-eucalyptol respectively indicating that all compounds, except quercetin, have more interactions with CXCR4 than with CXCR7. The structurally and functionally important residues in the interactive sites of docked CXCR4-complex and CXCR7-complex were identified. The ADME analysis showed that the compounds have drug-like properties. Only (1 s,4 s)-Eucalyptol has potential weak cardiotoxicity. The results of thermochemical and molecular orbital analysis and molecular dynamics simulation validated outcomes of molecular docking study. CONCLUSIONS: Curcumin showed the top binding interaction against active sites of CXCR4 and CXCR7 receptors, with the best safety profile, followed by quercetin, resveratrol, and eucalyptol. All compounds demonstrated drug-like properties. Eucalyptol has promising potential because it can be used by inhalation or skin massage. To our knowledge, this is the first attempt to find binding interactions of these natural agents with CXCR4 and CXCR7 receptors and to predict their druggability.

Structural analyses and classification of novel isoniazid resistance coupled mutational landscapes in Mycobacterium tuberculosis: a combined molecular docking and MD simulation study.

Drug resistance in Mycobacterium tuberculosis has become a major challenge to the current regime of treatment as well as to the containment of the disease globally. The molecular and genetic studies identified frequently occurring point mutations in the virulent protein such as KatG of M. tuberculosis resulted in the development of isoniazid tolerance in the pathogen. This study aims to analyze the structural basis of the disease mutations available in the literature as well as to predict novel alteration in the KatG which may cause similar deleterious effects. Around 15 experimentally derived mutations were included in this study and pathogenic mutational landscapes containing 60 site-specific alterations were predicted using the available in silico techniques. The effects of these mutations on the stability of the protein were studied and an exhaustive docking study was conducted for each classified perturbations, which identify the highest changes in the binding energies in p.Meth255Ile among experimental and p.Ala222Arg in computationally predicted mutations. Furthermore, the structural effects on these substitutions were analyzed using the principles of molecular dynamic simulations each for a 100 ns time scale, which validated the interaction studies. The outcome of this study may enable the identification of the novel drug resistance-associated point mutations which were not previously reported and may contribute significantly in a variety of experimental studies as well as facilitate the process of drug design and discovery.Communicated by Ramaswamy H. Sarma.

Tuning the anticancer properties of Pt(ii) complexes via structurally flexible N-(2-picolyl)salicylimine ligands.

Three tridentate Schiff base ligands were synthesized from the reactions between 2-picolylamine and salicylaldehyde derivatives (3-ethoxy (OEt), 4-diethylamino (NEt2) and 4-hydroxy (OH)). Complexes with the general formula Pt(N^N^O)Cl were obtained from reactions between the ligands and K2PtCl4. The ligands and their complexes were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. Further confirmation of the structure of Pt-OEt was achieved by single-crystal X-ray diffraction. The DMSO/chlorido exchange process at Pt-OEt was investigated by monitoring the change in conductivity, revealing very slow dissociation in DMSO. Moreover, solvent/chlorido exchange for Pt-OEt and Pt-NEt2 were investigated by NMR spectroscopy in DMSO and DMSO/D2O; Pt-NEt2 forms an adduct with DMSO while Pt-OEt forms adducts with DMSO and water. The DNA-binding behaviour of the platinum(ii) complexes was investigated by two techniques. Pt-NEt2 has the best apparent binding constant. The intercalation mode of interaction with ct-DNA was suggested by molecular docking studies and the increase in the relative viscosity of ct-DNA with increasing concentrations of the platinum(ii) complexes. However, the gradual decrease in the relative viscosity over time at constant concentration of platinum(ii) complexes indicated a shift from intercalation to a covalent binding mode. Anticancer activities of the ligands and their platinum(ii) complexes were examined against two cell lines. The platinum(ii) complexes exhibit superior cytotoxicity to that of their ligands. Among the platinum(ii) complexes, Pt-OEt possesses the best IC50 against both cell lines, its cytotoxicity being comparable to that observed for cisplatin. Cell cycle arrest in the HepG2 cell line upon treatment with Pt-OEt and Pt-NEt2 was investigated and compared to that of cisplatin; the change in the cell accumulation patterns supports the presumption of an apoptotic cell death pathway. The optimized structures of the B-DNA trimer adducts with the platinum complexes showed hydrogen-bonding interactions between the ligands and nucleobases, affecting the inter-strand hydrogen bonding within the DNA, and highlighting the strong ability of the complexes to induce conformational changes in the DNA, leading to the activation of apoptotic cell death. In summary, the current study demonstrates promising new anticancer platinum(ii) complexes with highly flexible tridentate ligands; the functional groups on the ligands are important in tuning their DNA binding/anticancer properties.

Novel saccharin analogs as promising antibacterial and anticancer agents: synthesis, DFT, POM analysis, molecular docking, molecular dynamic simulations, and cell-based assay.

Saccharine is a pharmacologically significant active scaffold for various biological activities, including antibacterial and anticancer activities. Herein, saccharinyl hydrazide (1) was synthesized and converted into 2-[(2Z)-2-(1,1-dioxo-1,2-dihydro-3H-1λ6,2- benzothiazole-3-ylidene) hydrazinyl] acetohydrazide (5), which was employed as a key precursor for synthesizing a novel series of small molecules bearing different moieties of monosaccharides, aldehydes, and anhydrides. Potent biological activities were found against Staphylococcus and Escherichia coli , and the results indicated that compounds 6c and 10a were the most active analogs with an inhibition zone diameter of 30-35 mm . In cell-based anticancer assay over Ovcar-3 and M-14 cell lines, compound 10a was the most potent analog with IC50 values of 7.64 ± 0.01 and 8.66 ± 0.01 µM, respectively. The Petra Orisis Molinspiration (POM) theoretical method was used to calculate the drug score of tested compounds and compare them with their experimental screening data. Theoretical DFT calculations were carried out in a gas phase in a set of B3LYP 6-311G (d,p). Molecular docking studies utilizing the MOE indicated the best binding mode with the highest energy interaction within the binding sites. The molecular docking for Ovcar-3 was carried out on the ovarian cancer protein (3W2S), while the molecular docking for M-14 melanoma was carried out on the melanoma cancer protein (2OPZ). The MD performed about 2ns simulations to validate selected compounds' theoretical studies.

Intravaginal administration of isosorbide mononitrate and misoprostol for cervical ripening and induction of labour: a randomized controlled trial.

BACKGROUND: Labor induction in the presence of unfavorable cervix is a common indication for the use of prostaglandins. However, in the last years, there has been a considerable interest in the use of nitrous oxide donors for cervical ripening and labor induction. OBJECTIVE: To evaluate the efficacy and safety of intravaginal administration of NOD isosorbide mononitrate (IMN) plus misoprostol versus misoprostol alone for cervical ripening and induction of labor. SETTING: Department of Obstetrics and Gynecology, Woman's Health Center, Assiut University. METHODS: Two hundred and ninety women scheduled for labor induction were recruited and assigned randomly to IMN or placebo followed by misoprostol 50 µg. The efficacy of the medication was evaluated by predetermined outcome variables for cervical ripening and induction of labor and delivery. RESULTS: The two groups were comparable with respect to age, parity, gestational age, indication for induction, and Bishop's score. Women receiving IMN plus misoprostol showed significant changes in the Bishop score 6 h after administration as compared to misoprostol plus placebo (8.57 ± 1.46 vs. 7.6 ± 1.39 h, P = 0.001), significantly shorter intervals from the beginning of the induction to the beginning of the active phase of labor (10.97 ± 2.87 vs. 13.91 ± 2.16 h, P = 0.0004) and from the beginning of induction to the time of delivery (19.56 ± 3.96 vs. 23 ± 2.62 P ≤ 0.001). No significant differences in the incidence of uterine hypersystole, tachysystole and hyperstimulation. Regarding headache, much more women suffer headache in the IMN group (51) with significant difference to placebo group (11). CONCLUSIONS: Using a combination of IMN and misoprostol is more efficient than misoprostol alone in terms of fast cervical ripening and shortening of induction-labour interval.

Practical and Computational Studies of Bivalence Metal Complexes of Sulfaclozine and Biological Studies.

In the search for novel, metal-based drug complexes that may be of value as anticancer agents, five new transition metal complexes of sulfaclozine (SCZ) with Cu(II), Co(II), Ni(II), Zn(II), and Fe(II) were successfully synthesized. The chemical structure of each complex was characterized using elemental analysis (CHN), IR spectroscopy, UV-Vis spectroscopy, thermogravimetric analysis (TGA), and electronic paramagnetic resonance (EPR) spectroscopy. IR spectra indicated that the donor atoms were one sulfonyl oxygen atom and one pyrazine nitrogen atom, which associated with the metal ions to form a stable hexagonal coordination ring. The metal-ligand stability constant (Kf) revealed that Cu(II) and Ni(II) have good coordination stability among the metal compounds. Theoretical studies using DFT/B3LYP were performed to further validate the proposed structures. The obtained results indicated that Cu(II) has a trigonal bipyramidal geometry, whereas Fe(II), Co(II), and Ni(II) have an octahedral structure, while Zn(II) has a tetrahedral arrangement. The bio-activities of the characterized complexes were evaluated using DNA binding titration and molecular docking. The binding constant values for the metal complexes were promising, with a maximum value for the copper metal ion complex, which was 9 × 105 M-1. Molecular docking simulations were also carried out to evaluate the interaction strength and properties of the synthesized metal complexes with both DNA and selected cancer-relevant proteins. These results were supported by in vitro cytotoxicity assays showing that the Cu(II) and Ni(II) complexes display promising antitumor activity against colon and breast cancer cell lines.

Complexation of uranyl (UO2)2+ with bidentate ligands: XRD, spectroscopic, computational, and biological studies.

Three new uranyl complexes [(UO2)(OAc)2(CMZ)], [(UO2)(OAc)2(MP)] and [(UO2)(OAc)2(SCZ)] were synthesized and characterized by elemental analysis, FT-IR, UV-Vis spectroscopy, powder XRD analysis, and molar conductivity. The IR analysis confirmed binding to the metal ion by the sulfur and ethoxy oxygen atoms in the carbimazole (CMZ) ligand, while in the 6-mercaptopurine (MP) ligand, the sulfur and the N7 nitrogen atom of a purine coordinated binding to the metal ion. The third ligand showed a 1:1 molar ratio and bound via sulfonamide oxygen and the nitrogen of the pyrimidine ring. Analysis of the synthesized complexes also showed that acetate groups had monodentate binding to the (UO22+). Density Functional Theory (DFT) calculations at the B3LYP level showed similar structures to the experimental results. Theoretical quantum parameters predicted the reactivity of the complexes in the order, [(UO2)(OAc)2(SCZ)] > [(UO2)(OAc)2(MP)]> [(UO2)(OAc)2(CMZ)]. DNA binding studies revealed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(CMZ)] have the highest binding constant (Kb) among the uranyl complexes. Additionally, strong binding of the MP and CMZ metal complexes to human serum albumin (HSA) were observed by both absorbance and fluorescence approaches. The antibacterial activity of the complexes was also evaluated against four bacterial strains: two gram-negative; Escherichia coli and Klebsiella pneumonia, and two gram-positive; Staphylococcus aureus and Streptococcus mutans. [(UO2)(OAc)2(MP)] had the greatest antibacterial activity against Klebsiella pneumonia, the gram-positive bacteria, with even higher activity than the standard antibiotic. In vitro cytotoxicity tests were also performed against three human cancer lines, and revealed the most cytotoxic complexes to be [(UO2)(OAc)2(SCZ)], which showed moderate activity against a colon cancer cell line. Thus, uranyl addition enhances the antibacterial and anticancer properties of the free ligands.