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The present investigation has been aimed to prepare and characterize, several cupper complexes containing [Cu(dafone)2(H2O)2]Cl (1), [Cu(dafone)2(en)]Cl2 (2) and [Cu(dafone)2(opd)]Cl2 (3) using FT-IR, UV–Vis techniques and elemental analysis. To understand the interaction of Cu(II) compounds with FS-DNA, different spectral methods have been employed. The binding constant (Kb) was determined by UV–Vis spectroscopy. The effective binding ability of metal compounds to DNA has been proved by the obtained results. The data related to fluorescence were achieved with the purpose of evaluating the binding and thermodynamic interaction parameters of copper (II) compounds with FS-DNA, at three various temperatures. According to the thermodynamic factors (∆S°, ∆H°, ∆G°), the major interaction concerning DNA- Cu(II) complexes are hydrogen bonding and van der Waals forces. Additionally, the binding constant (Kb) and the Stern–Volmer quenching constant (Ksv) of synthesized compounds and DNA were estimated. Measuring specific viscosity of FS-DNA showed no alterations considerably, whereas the concentration of copper(II) complexes enhanced. The groove binding mode is advocated by the viscosity data and circular dichroism. The synthesized compounds were further investigated against cancerous A549 (human lung adenocarcinoma), oral squamous carcinoma C152 (KB) cell lines and normal human umbilical vein endothelial (HUVEC) cells. Compounds 1 and 2 showed a good cytotoxicity activity against cancer cell lines while the IC50 values for normal cell line was about three times higher. The interaction mode of target compounds in DNA active site was investigated and confirmed the groove binding. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new formulation of hesperidin loaded solid lipid nanoparticles was developed and optimized by response surface method. • The optimized formulation was synthesized using hot homogenization and ultrasound and then characterized. • The optimized parameters produced small size (179.8 ± 3.6 nm) HESP-SLNs with high encapsulation efficiency (93.0 ± 3.8 %). • The anti-inflammatory effect via in vivo ear edema inflammation model exhibited that encapsulation in SLN carrier improves the anti-inflammatory potential of hesperidin. Hesperidin (C 28 H 34 O 15), a flavanone glycoside abundantly present in citrus fruits, has proven therapeutic effects including anti-inflammatory activities. Herein, we report a novel formulation of HESP loaded solid lipid nanoparticles (SLNs) using hot homogenization and ultrasound to improve the poor solubility and bioavailability. In the present study, the formulation was developed and optimized by response surface method and then characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy (FT-IR), and dynamic light scattering (DLS). Encapsulation efficiency was determined and the anti-inflammatory effect was assessed through in vivo ear edema inflammation model. According to the electron microscopy results, the product has a spherical shape. The optimized parameters produced small size (179.8 ± 3.6 nm) HESP-SLNs with high encapsulation efficiency (93.0 ± 3.8 %). The outcomes exhibited that encapsulation in SLNs carriers improves the anti-inflammatory potential of HESP. [ABSTRACT FROM AUTHOR]

A set of 1,2,4-triazine derivatives were designed as cyclooxygenase-2 (COX-2) inhibitors. These compounds were synthesized and screened for inhibition of cyclooxygenases (COX-1 and COX-2) based on a cellular assay using human whole blood (HWB) and lipoxygenase (LOX-15) that are key enzymes in inflammation. The results showed that 3-(2-(benzo[d][1,3]dioxol-5-ylmethylene)hydrazinyl)-5,6-bis(4-methoxyphenyl)-1,2,4-triazine (G11) was identified as the most potent COX-2 inhibitor (78%) relative to COX-1 (50%). Ferric reducing anti-oxidant power (FRAP) assay revealed that compound G10 possesses the highest anti-oxidant activity. The compound G3 with IC50value of 124 μM was the most potent compound in LOX inhibitory assay. Molecular docking was performed and a good agreement was observed between computational and experimental results. [ABSTRACT FROM PUBLISHER]

Cancer is a leading cause of death worldwide. Multidrug resistance (MDR) is a main reason of chemotherapy failure in many patients and is often related to overexpression of ATP-binding cassette (ABC) transporters, including P-glycoprotein (P-gp/ABCB1). Agents that are capable of modulation of the activity of these transporters might be effective in overcoming MDR. In this study, a new set of 1,4,5,6,7,8-hexahydro 5-oxo quinoline-3-carboxamide derivatives bearing 4-methylthiazole moiety and their tetrahydroquinoline counterparts were synthesized. MDR reversal activity of these 16 newly synthesized derivatives was tested in P-gp overexpressing MES-SA-DX5 human uterine sarcoma cells by flow cytometric determination of Rhodamine123 efflux. The effect of the most potent compounds in induction of apoptosis and alterations of cell cycle was examined in these cells by a flow cytometric method. Inherent cytotoxicity of the synthesized compounds was evaluated against MCF-7, A-549 and K562 cancer cell lines, as well as MES-SA-DX5 and their parental non-resistant MES-SA and also HEK-293 non-cancerous cells by MTT assay. Compounds A1 and A2 with 5-oxo-hexahydroquinoline structure bearing 2,4-dichlorophenyl and 4-bromophenyl moieties, respectively, and their tetrahydroquinoline counterparts B1 and B2 significantly blocked P-gp efflux, induced apoptosis and showed the highest cytotoxicities against MES-SA-DX5 cells. However, only A2 and B2 compounds were relatively selective against cancer and MDR cells as compared to non-resistant and non-cancerous cells. These findings demonstrate that 5-oxo-hexahydroquinoline and 5-oxo-tetrahydroquinoline derivatives represent promising agents with therapeutic potential in drug resistant cancers. [ABSTRACT FROM AUTHOR]

The synthesis of new derivatives of pyrrole substituted sulfonamide groups is described. The in vitro anticancer activity of these pyrroles was evaluated against MCF7, MOLT-4 and HL-60 cells using MTT assay. The target compounds showed inhibitory activity against tested cell lines. Among the compounds, compound 1a exhibited good cytotoxic activity. The potential of this analog to induce apoptosis was confirmed in a nuclear morphological assay by Hoechst 33258 staining in the PC-12 cells. Finally, molecular docking was performed to determine the probable binding mode of the designed pyrrole derivatives into the active site of FGFR1 protein. DFT calculations were carried out at the B3LYP levels of theory with 6-31+G (d,p) basis set for compound 1a . The point group (C 1 ) of it was obtained based on the optimized structures; the calculation of the FT-IR vibrational frequencies, 1 H NMR and 13 C NMR chemical shifts of the compound were carried out and compared with those obtained experimentally. [ABSTRACT FROM AUTHOR]

Objective: Assessment of the cytotoxicity of novel calcium silicate-based cement is imperative in endodontics. This experimental study aimed to assess the cytotoxicity and odontogenic/osteogenic differentiation potential of a new calcium silicate/pectin cement called Nano-dentine against stem cells from the apical papilla (SCAPs). Materials and Methods: In this experimental study, the cement powder was synthesized by the sol-gel technique. Zirconium oxide was added as opacifier and Pectin, a plant-based polymer, and calcium chloride as the liquid to prepare the nano-based dental cement. Thirty-six root canal dentin blocks of human extracted single-canal premolars with 2 mm height, flared with #1, 2 and 3 Gates-Glidden drills were used to prepare the cement specimens. The cement, namely mineral trioxide aggregate (MTA), Biodentine, and the Nano-dentine were mixed according to the manufacturers’ instructions and applied to the roots of canal dentin blocks. The cytotoxicity and odontogenic/osteogenic potential of the cement were evaluated by using SCAPs. Results: SCAPs were characterized by the expression of routine mesenchymal cell markers and differentiation potential to adipocytes, osteoblasts, and chondrocytes. Cement displayed no significant differences in cytotoxicity or calcified nodules formation. Gene expression analysis showed that all three types of cement induced significant downregulation of COLA1; however, the new cement induced significant up-regulation of RUNX2 and SPP1 compared to the control group and MTA. The new cement also induced significant up-regulation of TGFB1 and inducible nitric oxide synthase (iNOS) compared with Biodentine and MTA. Conclusion: The new Nano-dentin cement has higher odontogenic/osteogenic potential compared to Biodentine and MTA for differentiation of SCAPs to adipocytes, osteoblasts, and chondrocytes. [ABSTRACT FROM AUTHOR]

Background: It is known that severe acute respiratory coronavirus 2 (SARS-CoV-2) is the viral strain responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Current documents have demonstrated that the virus causes a PGE2 storm in a substantial proportion of patients via upregulating cyclooxygenase-2 (COX-2) and downregulating prostaglandin E2 (PGE2)-degrading enzymes within the host cell. Aim: Herein, we aimed to study how short-term treatment with celecoxib (Celebrex), a selective COX-2 inhibitor, affects demographic features, early symptoms, O2 saturation, and hematological indices of cases with COVID-19. Methods: A total of 67 confirmed COVID-19 cases with a mild or moderate disease, who had been referred to an institutional hospital in south-eastern Iran from October 2020 to September 2021, were enrolled. Demographic characteristics, symptoms, and hematological indices of the patients were recorded within different time periods. One-way ANOVA or Kruskal–Wallis tests were used to determine differences between data sets based on normal data distribution. Results: O2 saturation was statistically different between the control group and patients receiving celecoxib (p = 0.039). There was no marked difference between the groups in terms of the symptoms they experienced (p > 0.05). On the first days following Celebrex therapy, analysis of complete blood counts showed that white blood cell (WBC) counts were markedly lower in patients treated with a high dose of celecoxib (0.4 g/day) than in controls (p = 0.026). However, mean lymphocyte levels in patients receiving a high dose of celecoxib (0.4 g/day) were markedly higher than in patients receiving celecoxib with half of the dose (0.2 g/day) for one week or the untreated subjects (p = 0.004). Changes in platelet count also followed the WBC alteration pattern. Conclusion: Celecoxib is a relatively safe, inexpensive, and widely available drug with non-steroidal anti-inflammatory properties. The therapeutic efficacy of celecoxib depends on the administrated dose. Celecoxib might improve disease-free survival in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Almost a century after the devastating pandemic of the Spanish flu, humankind is facing the relatively comparable global outbreak of COVID‐19. COVID‐19 is an infectious disease caused by SARS‐CoV‐2 with an unprecedented transmission pattern. In the face of the recent repercussions of COVID‐19, many have argued that the clinical experience with influenza through the last century may have tremendous implications in the containment of this newly emerged viral disease. During the last 2 years, from the emergence of COVID‐19, tremendous advances have been made in diagnosing and treating coinfections. Several approved vaccines are available now for the primary prevention of COVID‐19 and specific treatments exist to alleviate symptoms. The present review article aims to discuss the pathophysiology, diagnosis, and treatment of SARS‐CoV‐2 and influenza A virus coinfection while delivering a bioinformatics‐based insight into this subject matter. [ABSTRACT FROM AUTHOR]

• A multicomponent reaction (MCR) of amino acids, aldehydes, β-dicarbonyl compounds, and malononitrile was applied of a novel class of dihydropyridinium scaffolds which are incorporating amino acid moieties. • The reaction proceeded through formation of a stable enolate as triethylammoniumenolate salt. • The DFT calculations confirm the stability of the formed dihydropyridinium structure. • The docking studies of the synthesized compounds on the acetylcholinesterase show high potential inhibitory activities of these compounds in Alzheimer's disease. In this study, a multicomponent reaction (MCR) of amino acids, aldehydes, β-dicarbonyl compounds, and malononitrile is presented to obtain a novel class of dihydropyridinium scaffolds which are incorporating amino acid moieties. Some derivatives were obtained in tetrahydropyrido[2,3- d ]pyrimidin form. The reaction proceeded through formation of a stable enolate as triethylammoniumenolate salt, which is isolable from the reaction mixture. The DFT calculations also confirm the stability of the formed dihydropyridinium structure. The docking studies of the synthesized compounds on the acetylcholinesterase target (PDB ID = 5FUM) show high potential inhibitory activities of these compounds in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Since early 2020, COVID-19 has wreaked havoc in many societies around the world. As of the present, the SARS-CoV-2-borne disease is propagating in almost all countries, affecting hundreds of thousands of people in an unprecedented way. As the name suggests, the novel coronavirus, widely known as SARS-CoV-2, is a new emerging human pathogen. A novel disease of relatively unknown origin, COVID-19 does not seem to be amenable to the currently available medicines since there is no specific cure for the disease. In the absence of any vaccine or effective antiviral medication, we have no tools at our disposal, but the method of quarantine, be it domestic or institutional, to hinder any further progression of this outbreak. However, there is a record of physicians in the past who practiced convalescent blood transfusion. To their awe, the method seemed to be useful. It is anticipated that these contemporary methods will outdo any other vaccination process in the time being, as blood transfusion is instead a cost-effective and time-friendly technique. Following a successful trial, this new approach of contemporary nature to a viral disease may serve as an emergency intervention to intercept infectious outbreaks and prevent an impending epidemic/pandemic. In this review, we document the most recent evidence regarding the efficiency of convalescent plasma and serum therapy on SARS, MERS, and particularly COVID-19, while discussing potential advantages and possible risks of such practice. [ABSTRACT FROM AUTHOR]

Autophagy‐dependent cell death is a prominent mechanism that majorly contributes to homeostasis by maintaining the turnover of organelles under stressful conditions. Several viruses, including coronaviruses (CoVs), take advantage of cellular autophagy to facilitate their own replication. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a beta‐coronavirus (β‐CoVs) that mediates its replication through a dependent or independent ATG5 pathway using specific double‐membrane vesicles that can be considered as similar to autophagosomes. With due attention to several mutations in NSP6, a nonstructural protein with a positive regulatory effect on autophagosome formation, a potential correlation between SARS‐CoV‐2 pathogenesis mechanisms and autophagy can be expected. Certain medications, albeit limited in number, have been indicated to negatively regulate autophagy flux, potentially in a way similar to the inhibitory effect of β‐CoVs on the process of autophagy. However, there is no conclusive evidence to support their direct antagonizing effect on CoVs. Off‐target accumulation of a major fraction of FDA‐approved autophagy modulating drugs may result in adverse effects. Therefore, medications that have modulatory effects on autophagy could be considered as potential lead compounds for the development of new treatments against this virus. This review discusses the role of autophagy/virophagy in controlling SARS‐CoV‐2, focusing on the potential therapeutic implications. [ABSTRACT FROM AUTHOR]

[Display omitted] • Methylxanthine derivatives exert different biological properties. • Three previously synthesized 8-alkylmercaptocaffeine derivatives showed desirable cytotoxic activity through the cGMP pathway. • Computational studies showed that these derivatives could bind to the catalytic domain of PDE enzymes. • Our findings highlight the role of methylxanthines as useful alternatives to conventional cancer therapeutics. Due to their unique pharmacological characteristics, methylxanthines are known as therapeutic agents in a fascinating range of medicinal scopes. In this report, we aimed to examine some biological effects of previously synthesized 8-alkylmercaptocaffeine derivatives. Cytotoxic and antioxidative activity of 8-alkylmercaptocaffeine derivatives were measured in malignant A549, MCF7, and C152 cell lines. Assessment of cGMP levels and caspase-3 activity were carried out using a colorimetric competitive ELISA kit. Computational approaches were employed to discover the inhibitory mechanism of synthesized compounds. Among the twelve synthesized derivatives, three compounds (C1, C5, and C7) bearing propyl, heptyl, and 3-methyl-butyl moieties showed higher and more desirable cytotoxic activity against all the studied cell lines (IC 50 < 100 µM). Furthermore, C5 synergistically enhanced cisplatin-induced cytotoxicity in MCF-7 cells (CI < 1). Both C5 and C7 significantly increased caspase-3 activity and intracellular cGMP levels at specific time intervals in all studied cell lines (P < 0.05). However, these derivatives did not elevate LDH leakage (P > 0.05) and exhibited no marked ameliorating effects on oxidative damage (P > 0.05). Computational studies showed that H-bond formation between the nitrogen atom in pyrazolo[4,3-D] pyrimidine moiety with Gln817 and creating a hydrophobic cavity result in the stability of the alkyl group in the PDE5A active site. We found that synthesized 8-alkylmercaptocaffeine derivatives induced cell death in different cancer cells through the cGMP pathway. These findings will help us to get a deeper insight into the role of methylxanthines as useful alternatives to conventional cancer therapeutics. [ABSTRACT FROM AUTHOR]

A most discussed topic of the new decade, COVID-19 is an infectious disease caused by the recently discovered SARS-CoV-2. With an exceedingly high transmission rate, COVID-19 has affected almost all the countries in the world. Absent any vaccine or specific treatment, the humanity is left with nothing but the legacy method of quarantine. However, quarantine can only be effective when combined with early diagnosis of suspected cases. With their high sensitivity and unmatched specificity, biosensors have become an area of interest for development of novel diagnostic methods. Compared to the more traditional diagnostics, nanobiotechnology introduces biosensors as different diagnostics with greater versatility in application. Today, a growing number of analytes are being accurately identified by these nanoscopic sensing machines. Several reports of validated application with real samples further strengthen this idea. As of recent, there has been a rise in the number of studies on portable biosensors. Despite the slow progression, certain devices with embedded biosensors have managed to be of diagnostic value in several countries. The perceptible increase in development of mobile platforms has revolutionized the healthcare delivery system in the new millennium. The present article reviews the most recent advancements in development of diagnostic nanobiosensors and their application in the clinical fields. Key points: • There is no specific treatment for highly transmissible SARS-CoV-2. • Early diagnosis is critical for control of pandemic. • Highly sensitive/specific nanobiosensors are emerging assets against COVID-19. [ABSTRACT FROM AUTHOR]

Months after the outbreak of a new flu‐like disease in China, the entire world is now in a state of caution. The subsequent less‐anticipated propagation of the novel coronavirus disease, formally known as COVID‐19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS‐CoV‐2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID‐19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed. [ABSTRACT FROM AUTHOR]

Abstract: A concise, clean synthetic approach to access of 2,5-dihydro-1H-pyrrole-2-carboxylates by two-component condensation reaction of ethyl pyruvate and aniline derivatives under catalyst-free and solvent-free conditions is described. The advantages of this method are practical simplicity, catalyst-free and solvent-free conditions, high atom economy, short reaction times, and good yields of the products. The anticancer potential of synthesized compounds was evaluated against MCF7, MOLT-4 and HL-60 cells by using MTT assay. Among the tested synthesized 2,5-dihydro-1H-pyrrole-2-carboxylates (3a-h, 4a-d), compound 4d having sulfonamide moiety exhibited good cytotoxic activity against all tested cell lines and molecular docking studies also demonstrated that the results of the docking study are in reasonable agreement with cytotoxicity activities.Graphical Abstract: A series of 2,5-dihydro-1H-pyrrole-2-carboxylate derivatives were synthesized by two-component condensation reaction of ethyl pyruvate and aniline derivatives under catalyst-free and solvent-free conditions. [ABSTRACT FROM AUTHOR]

A compound of [Au(5,5′-dmbpy)(Cl)2] (where dmbpy is 5,5′-Dimethyl-2,2′-bipyridine). The interaction of reported complex with DNA was systematically studied by different spectroscopic techniques. The obtained cytotoxicity results suggested that the target complex could be proved via further studies as potential antitumor agents. [Display omitted] A novel gold complex: [Au(5 5´-dmbipy)(Cl) 2 ] (a) which dmbipy is 5 5́-Dimethyl-2 2́-bipyridine has been synthesized and different techniques were applied to confirm the chemical structure. The structure consists of a gold cation chelated by one neutral bipyridine ligand two (Cl-) ions and one (Cl-) ion inside and outside of the coordination sphere respectively. Thermodynamic parameters (ΔH° ΔS° and ΔG°) calculated from FS-DNA interaction of complex showed that electrostatic binding have an essential function in the interaction of DNA–Au(III) complex. Additionally relative viscosity of DNA did not change while the concentration increased. As proved by Circular dichroism (CD) spectra the DNA structure changed. Interestingly the synthesized compound exhibited an effective cytotoxic behavior against cancerous cell lines. The molecular docking exploration indicated the non-intercalative mode of binding which confirms the obtained results from spectroscopy viscometry and CD techniques. [ABSTRACT FROM AUTHOR]

• A compound of {[Ni(5,5´-dmbipy)3](SCN)2}2 a1 was synthesized and characterized by FT-IR, UV–Vis spectroscopy, elemental analysis, luminescence and X-ray crystallography. • Thermodynamic parameters (∆H°, ΔS° and ΔG°) calculated from FS-DNA interaction of complexes showed that hydrogen bonding and van der Waals interactions have an essential function in stability. • The antibacterial properties were investigated in vitro against standard Gram-positive and Gram-negative bacterial strains • The cytotoxicity activity experiments against MCF-7, KB and A549 cells revealed low to moderate antiproliferative activity • Molecular docking results confirmed the spectroscopic and viscosity titration outcomes. A compound of {[Ni(5,5´-Dimethyl-2,2´-bipyridine) 3 ](SCN) 2 } 2 (a) was synthesized and characterized by FT-IR, UV–Vis spectroscopy, elemental analysis, luminescence and X-ray crystallography. The single crystals were obtained by slow crystallization from a methanol solution. The complex is composed of nickel cation chelated by three neutral bipyridine ligands and two (SCN−) ions outside the coordination sphere. The nano form of the synthesized complex (b) was prepared by a sonochemical process and confirmed with XRD, SEM and FT-IR. The average size of the particles was 37 nm from SEM. Thermodynamic parameters (∆H°, ΔS° and ΔG°) calculated from FS-DNA interaction of complexes showed that hydrogen bonding and van der Waals interactions have an essential function in the interaction of DNA–Ni(II) complex, and the interaction mode is groove binding. Viscosity measurement illustrated that relative viscosity of DNA remained unchanged with the adding concentrations of complexes. Circular dichroism (CD) spectra showed that the structure of DNA was changed. The antibacterial properties were investigated in vitro against standard Gram-positive and Gram-negative bacterial strains. The results of antibacterial tests showed that (a) was a stronger antibacterial agent than the free ligand, and that the antibacterial effect of (b) was stronger than the one of (a). The cytotoxicity activity experiments against MCF-7, KB and A549 cells revealed low to moderate antiproliferative activity of the complex (b) against cancer cells. The molecular docking results exhibited groove mode of binding, confirming previously obtained data from spectroscopy, viscometry and CD. Image, graphical abstract [ABSTRACT FROM AUTHOR]