Synthesis, Characterization, DFT Studies of Novel Cu(II), Zn(II), VO(II), Cr(III), and La(III) Chloro-Substituted Schiff Base Complexes: Aspects of Its Antimicrobial, Antioxidant, Anti-Inflammatory, and Photodegradation of Methylene Blue.

A new chlorobenzylidene imine ligand, (E)-1-((5-chloro-2-hydroxybenzylidene)amino) naphthalen-2-ol (HL), and its [Zn(L)(NO3)(H2O)3], [La(L)(NO3)2(H2O)2], [VO(L)(OC2H5)(H2O)2], [Cu(L)(NO3)(H2O)3], and [Cr(L)(NO3)2(H2O)2], complexes were synthesized and characterized. The characterization involved elemental analysis, FT-IR, UV/Vis, NMR, mass spectra, molar conductance, and magnetic susceptibility measurements. The obtained data confirmed the octahedral geometrical structures of all metal complexes, while the [VO(L)(OC2H5)(H2O)2] complex exhibited a distorted square pyramidal structure. The complexes were found to be thermally stable based on their kinetic parameters determined using the Coats-Redfern method. The DFT/B3LYP technique was employed to calculate the optimized structures, energy gaps, and other important theoretical descriptors of the complexes. In vitro antibacterial assays were conducted to evaluate the complexes' potential against pathogenic bacteria and fungi, comparing them to the free ligand. The compounds exhibited excellent fungicidal activity against Candida albicans ATCC: 10231 (C. albicans) and Aspergillus negar ATCC: 16404 (A. negar), with inhibition zones of HL, [Zn(L)(NO3)(H2O)3], and [La(L)(NO3)2(H2O)2] three times higher than that of the Nystatin antibiotic. The DNA binding affinity of the metal complexes and their ligand was investigated using UV-visible, viscosity, and gel electrophoresis methods, suggesting an intercalative binding mode. The absorption studies yielded Kb values ranging from 4.40 × 105 to 7.30 × 105 M-1, indicating high binding strength to DNA comparable to ethidium bromide (value 107 M-1). Additionally, the antioxidant activity of all complexes was measured and compared to vitamin C. The anti-inflammatory efficacy of the ligand and its metal complexes was evaluated, revealing that [Cu(L)(NO3)(H2O)3] exhibited the most effective activity compared to ibuprofen. Molecular docking studies were conducted to explore the binding nature and affinity of the synthesized compounds with the receptor of Candida albicans oxidoreductase/oxidoreductase INHIBITOR (PDB ID: 5V5Z). Overall, the combined findings of this work demonstrate the potential of these new compounds as efficient fungicidal and anti-inflammatory agents. Furthermore, the photocatalytic effect of the Cu(II) Schiff base complex/GO was examined.

Electrospun PVA nanofiber mat for topical Deflazacort delivery: accentuated anti-inflammatory efficacy for wound healing.

PURPOSE: Asses the wound healing activity of Polyvinyl alcohol - Deflazacort (PVA-DEF) nanofibers mats synthesized by electrospinning technology. METHODS: PVA-DEF nanofiber mats were created with various PVA polymer concentrations using an electrospinning process. The morphological features and diameter of the electrospun nanofibrous mats were investigated using scanning electron microscopy (SEM). The in vitro DEF release rate from PVA electrospun nanofibrous mats was evaluated. In addition to assessing wound healing activity in vivo, histological, and immunochemical tests were conducted. RESULTS: Results revealed a uniform and smooth surface of the fiber with an average diameter of the selected fibers of 533.9 nm ± 45.83. Also, PVA electrospun nanofiber mats showed an initial burst release of more than 50% of the DEF in 1 h, and the rest of the DEF was released gradually for up to 480 min. Fickian diffusion is the main DEF release mechanism from PVA electrospun nanofiber mats. In male Wistar albino rats with 1 cm2 excision wounds, in vivo studies revealed a significant improvement in wound healing rate via modulation of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) expression. CONCLUSION: PVA-DEF nanofiber mats can be used effectively for improving wound healing.

Synthesis, structural characterization, and biological studies of ATBS-M complexes (M(II) = Cu, Co, Ni, and Mn): Access for promising antibiotics and anticancer agents.

A new bidentate Schiff base ligand (ATBS [4-bromo-2-(thiazole-2-yliminomethyl)phenol]) was synthesized via the condensation reaction of 2-aminothiazole with 5-bromosalicylaldehyde in ethanol. The reaction of ATBS with transition metal salts of Cu(II), Co(II), Ni(II), and Mn(II) afforded the corresponding ATBS-M complexes. Results from physicochemical and spectral analyses, such as elemental analysis, infrared, UV-Vis spectroscopy, magnetic susceptibility, and molar conductance, revealed a nonelectrolytic nature with octahedral (Oh ) geometry and a metal/ligand ratio of 1:2 for Cu(II), Co(II), and Ni(II), but 1:1 for the Mn(II) complex. The density functional theory (DFT) calculations are correlated very well with the proposed structure and molecular geometry of the complexes as [M(ATBS)2 ] (M = Cu, Co, and Ni) and [Mn(ATBS)(H2 O)2 ]. Significantly, the prepared compounds showed strong inhibition activity for a wide spectrum of bacteria (Escherichia coli, Bacillus subtilis, and Staphylococcus aureus) and fungi (Candida albicans, Aspergillus flavus, and Trichophyton rubrum), with the ATBS-Ni complex being the most promising antibiotic agent. Molecular docking studies of the binding interaction between the title complexes with the bacterial protein receptor CYP51 revealed clear insights about the inhibition nature against the studied microorganisms, with the following order: ATBS-Cu > ATBS-Mn > ATBS-Ni > ATBS-Co for complex stability. Moreover, the cytotoxicity measurements of all prepared metal complexes against the colon carcinoma (HCT-116) and hepatocellular carcinoma (Hep-G2) cell lines showed exceptional anticancer efficacy of the complexes as compared with the free ATBS Schiff base ligand. Significantly, the results attested that ATBS-Cu is the most effective complex against HCT-116 cells, whereas ATBS-Mn has the highest cytotoxic efficiency against Hep-G2 cells. Furthermore, electronic spectra, viscosity measurements, and gel electrophoresis techniques were employed to probe the interaction of all prepared ATBS-metal complexes with calf thymus (CT)-DNA. Results confirmed that all complexes are strongly bound to CT-DNA via intercalation mode, with the ATBS-Co complex having the highest binding ability.

Synthesis, DFT Calculations, Antiproliferative, Bactericidal Activity and Molecular Docking of Novel Mixed-Ligand Salen/8-Hydroxyquinoline Metal Complexes.

Despite the common use of salens and hydroxyquinolines as therapeutic and bioactive agents, their metal complexes are still under development. Here, we report the synthesis of novel mixed-ligand metal complexes (MSQ) comprising salen (S), derived from (2,2'-{1,2-ethanediylbis[nitrilo(E) methylylidene]}diphenol, and 8-hydroxyquinoline (Q) with Co(II), Ni(II), Cd(II), Al(III), and La(III). The structures and properties of these MSQ metal complexes were investigated using molar conductivity, melting point, FTIR, 1H NMR, 13C NMR, UV-VIS, mass spectra, and thermal analysis. Quantum calculation, analytical, and experimental measurements seem to suggest the proposed structure of the compounds and its uncommon monobasic tridentate binding mode of salen via phenolic oxygen, azomethine group, and the NH group. The general molecular formula of MSQ metal complexes is [M(S)(Q)(H2O)] for M (II) = Co, Ni, and Cd or [M(S)(Q)(Cl)] and [M(S)(Q)(H2O)]Cl for M(III) = La and Al, respectively. Importantly, all prepared metal complexes were evaluated for their antimicrobial and anticancer activities. The metal complexes exhibited high cytotoxic potency against human breast cancer (MDA-MB231) and liver cancer (Hep-G2) cell lines. Among all MSQ metal complexes, CoSQ and LaSQ produced IC50 values (1.49 and 1.95 µM, respectively) that were comparable to that of cisplatin (1.55 µM) against Hep-G2 cells, whereas CdSQ and LaSQ had best potency against MDA-MB231 with IC50 values of 1.95 and 1.43 µM, respectively. Furthermore, the metal complexes exhibited significant antimicrobial activities against a wide spectrum of both Gram-positive and -negative bacterial and fungal strains. The antibacterial and antifungal efficacies for the MSQ metal complexes, the free S and Q ligands, and the standard drugs gentamycin and ketoconazole decreased in the order AlSQ > LaSQ > CdSQ > gentamycin > NiSQ > CoSQ > Q > S for antibacterial activity, and for antifungal activity followed the trend of LaSQ > AlSQ > CdSQ > ketoconazole > NiSQ > CoSQ > Q > S. Molecular docking studies were performed to investigate the binding of the synthesized compounds with breast cancer oxidoreductase (PDB ID: 3HB5). According to the data obtained, the most probable coordination geometry is octahedral for all the metal complexes. The molecular and electronic structures of the metal complexes were optimized theoretically, and their quantum chemical parameters were calculated. PXRD results for the Cd(II) and La(III) metal complexes indicated that they were crystalline in nature.

Trans-cinnamaldehyde Modulates Hippocampal Nrf2 Factor and Inhibits Amyloid Beta Aggregation in LPS-Induced Neuroinflammation Mouse Model.

Trans-cinnamaldehyde (CNM) has recently drawn attention due to its potent anti-inflammatory and antioxidant properties. The current study explored the memory enhancing effects of CNM against lipopolysaccharide (LPS)-induced neuroinflammation in mice. CNM and curcumin (a reference antioxidant) were administered at a dose of 50 mg/kg i.p. 3 h after a single LPS injection (0.8 mg/kg, i.p.) and continued daily for 7 days. Our results displayed that CNM and curcumin significantly ameliorated the LPS-induced impairment of learning and memory, neuroinflammation, oxidative stress and neuronal apoptosis. Memory functions and locomotor activity were assessed by Morris water maze, object recognition test and open field test. Both CNM and curcumin activated the nuclear factor erythroid 2 related factor 2 (Nrf2) and restored levels of downstream antioxidant enzymes superoxide dismutase and glutathione-S-transferase (GST) in the hippocampus. They also attenuated LPS-induced increase in hippocampal contents of interleukin-1ß (IL-1ß), malondialdehyde and caspase-3. Immunohistochemistry results showed that both CNM and curcumin reduced Aß1-42 protein accumulation in brain of mice. Remarkably CNM's effect on IL-1ß was less pronounced than curcumin; however it showed higher GST activity and more potent anti-apoptotic and anti-amylodogenic effect. We conclude that, CNM produces its memory enhancing effects through modulation of Nrf2 antioxidant defense in hippocampus, inhibition of neuroinflammation, apoptosis and amyloid protein burden.

Enhanced In Vivo Wound Healing Efficacy of a Novel Hydrogel Loaded with Copper (II) Schiff Base Quinoline Complex (CuSQ) Solid Lipid Nanoparticles.

Wound dressings created using nanotechnology are known as suitable substrates to speed up the healing of both acute and chronic wounds. Therapeutic substances can be delivered using these materials. In this study, a hydrogel loaded with Cu (II) Schiff base 8-hydroxy quinoline complex (CuSQ) solid lipid nanoparticles (SLN) was formulated to investigate its wound healing potential in an excision wound healing model in rats. The CuSQ SLN were spherical shaped with sizes ranging from 111 to 202 nm and a polydispersity index (PDI) ranging from 0.43 to 0.76, encapsulation efficiency (EE) % between 85 and 88, and zeta potential (ZP) of -11.8 to -40 mV. The formulated hydrogel showed good homogeneity, good stability, and a pH of 6.4 which indicates no skin irritation and had no cytotoxicity on the human skin fibroblast (HSF) cell line. In the in vivo study, animals were placed in five groups: control, standard, plain hydrogel, low dose, and high dose of CuSQ hydrogel. Both doses of CuSQ showed significantly faster healing rates compared to standard and control rats. In addition, the histopathology study showed more collagen, improved angiogenesis, and intact re-epithelization with less inflammation. A significant increase in transforming growth factor-beta1 (TGF-ß1) level and increased immune expression of vascular endothelial growth factor (VEGF) by CuSQ treatment validates its role in collagen synthesis, proliferation of fibroblasts and enhancement of angiogenesis. Matrix metalloproteinase-9 (MMP-9) was found to be significantly reduced after CuSQ treatment. Immunohistochemistry of tumor necrosis factor alpha (TNF-α) revealed a marked decrease in inflammation. Thus, we concluded that CuSQ would be a beneficial drug for cutaneous wound healing since it effectively accelerated wound healing through regulation of various cytokines and growth factors.

Amelioration of autoimmunity and inflammation by zinc oxide nanoparticles in experimental rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the lining of the synovial joints and approximately affects 0.5 - 1% of the total population imposing a socioeconomic burden. The current study aimed at investigating the novel possible beneficial effects of using zinc oxide nanoparticles (ZnO NPs) on such devastating disease. The complete Freund's adjuvant (CFA) model was used to mimic RA in rats where ZnO NPs were given orally (2 mg/kg/day) daily for 14 days; and diclofenac Na, the standard drug, was given intraperitoneally (1 mg/kg/day) the day after CFA, daily for 14 days. Our results displayed that ZnO NPs attenuated adjuvant-induced increased production of inflammatory mediators interleukin-1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), and total leukocyte count. Besides, they ameliorated autoimmunity through suppression of anti-citrullinated protein auto antibodies (anti-CCP) levels in rats. In conclusion our results highlight the benefits which could be obtained of nanoparticles either alone or in combination with the known anti-arthritic and/or anti-inflammatory agents, giving rise to new protocols to maximize the control of RA.

Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti-Inflammatory Agents.

The synthesis of a novel and attractive class of nonsteroidal anti-inflammatory and antimicrobial organoiron dendrimers attached to the well-known drug ibuprofen is achieved. The structures of these dendrimers are established by spectroscopic and analytical techniques. The antimicrobial activity of these dendrimers is investigated and tested against five human pathogenic Gram-positive and Gram-negative bacteria, and minimum inhibitory concentrations are reported. Some of these synthesized dendrimers exhibit higher inhibitory activity against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Staphylococcus warneri compare to the reference drugs. As well, the in vitro and in vivo anti-inflammatory activities of these dendrimers are evaluated. The results of in vivo anti-inflammatory activity and histopathology of inflamed paws show that all dendrimers display considerable anti-inflammatory activity; however, second-generation dendrimer (G2-D6) shows the best anti-inflammatory activity, which is more potent than the commercial drug ibuprofen at the same tested dose. Results of the toxicity study reveal that G2-D6 is the safest drug on biological tissues.