Folate deprivation induced neuroinflammation impairs cognition.

Nutritional status is associated with many neurocognitive diseases. Folate is one of the micronutrients, and its deficiency is associated with clinical outcomes of neurological diseases. Nevertheless, molecular mechanism behind the folate deficiency induced neurological disorders are not well-known. We have hypothesized that folate-deficiency is a cardinal determinant responsible for manifestation of cognitive impairment through inflammation mediated neurodegenerative pathologies. Objective of the current study was to assess whether folate deficiency is associated with cognitive dysfunction or is merely an epiphenomenon and to identify the underlying mechanisms. We developed folate insufficient zebrafish model through intra-peritoneal treatment of methotrexate. T-maze test was carried to assess the spatial learning and memory of the fish. Higher latency of the folate-deprived zebrafishes in the T-maze test is a reflection of altered cognition. This result is supported by declined levels of dopamine and serotonin, neurotransmitters linked with learning and memory. Elevated IL-6 and CRP in peripheral blood, along with increased expression of NF-ĸB in brain indicates manifestation of neuroinflammation. Indeed, together with upregulation of maptb gene it can be implied that folate deficiency acts as a risk factor for neurodegeneration in the form of tauopathies. Furthermore, diminished localisation of synaptopodin, a protein linked to neural plasticity, suggests that neuroinflammation caused by folate deprivation hampers the plasticity of brain. Histological analysis of brain revealed the development of histopathological features including spongiform degeneration and neuronal loss in folate deprived condition. We thus conclude that folate deficiency results in NF-ĸB activation, which through multiple processes mediated by neuroinflammation could lead to cognitive decline.

Synthesis of Calix-Salen Silver Corates for Evaluation of Their Antimicrobial and Anticancer Activities.

Silver-based products are becoming popular as antimicrobial agents because of the failure of antibiotics available for tackling the drug-resistant microbial strains. As silver is well tolerated by normal human cells, silver complexes have emerged as important antineoplastic agents. Further, if silver ions are encapsulated within an organic molecule-an azacorand-it may serve as a better substitute for cisplatin or other metal complexes. The calix-salen-type corates were synthesized using silver ions as the template. 5,5'-methylene-bis-salicylaldehyde was reacted with ethylene diamine in methanol at room temperature in the presence of silver nitrate. The resultant corand trapped the silver template in their cavity. The electron-withdrawing and electron-releasing groups like -NO2, -Br, -C(CH3)3, and -OCH3 were substituted on the bis-aldehyde to study their effects on the antimicrobial and anticancer activities of silver corates. The silver corates were found to have better antimicrobial activity than some of the standard drugs. Bromo-substituted corate-3, nitro-substituted corate-4, and tert-butyl-substituted corate-5 were found to be potent antibacterial agents among all. The bromo-substituted corate-3 was found to be the most potent fungicidal agent among all silver corates. The result of antineoplastic activity suggests that unsubstituted corate-1 and bromo-substituted corate-3 are potential candidates to be used as therapeutic molecules for cancer treatment, which requires further validation.

Phenolate based metallomacrocyclic xanthate complexes of Co(II)/Cu(II) and their exclusive deployment in [2 : 2] binuclear N,O-Schiff base macrocycle formation and in vitro anticancer studies.

Potassium salts of phenolate based polydentate xanthate ligands 4,4'-bis(2-dithiocarbonatobenzylideneamino)diphenyl ether () and 4,4'-bis(2-dithiocarbonatonaphthylmethylideneamino)diphenyl ether () have been synthesized and characterized, prior to use. The reaction of or with M(OAc)2 in Et3N affords access to a rare series of binuclear metallomacrocyclic xanthate complexes of the type [M2-µ(2)-bis-(κ(2)S,S-xan(1)/xan(2))] () which quickly forms [2 : 2] binuclear N,O-bidentate Schiff base macrocyclic complexes of the type [M2-µ(2)-bis-(κ(2)N,O-L(1)/L(2))] ( = 4,4'-bis(2-hydroxybenzylideneamino)diphenyl ether, = 4,4'-bis(2-hydroxynaphthylmethylidene-amino)diphenyl ether) via evolution of CS2 in solution. The compounds were characterized by microanalysis, relevant spectroscopy (FT-IR, UV-visible), mass spectrometry (ESI-MS), and powder and single crystal XRD techniques. In vitro anticancer activity of all the compounds was evaluated against HEP 3B (hepatoma) and IMR 32 (neuroblastoma) by the MTT assay. Remarkably, the binuclear copper(ii) xanthate complexes were found to be extremely active against both the cell lines (IC50: 8.1 ± 0.8 µM (), 8.8 ± 1.7 µM () against HEP 3B and 1.9 ± 0.3 µM () and 7.3 ± 0.6 µM () against IMR 32) and this projects them as good candidates for potent antitumor agents and the IC50 values confirm their better potency than the reference drug cisplatin. The flow-cytometric density plot illustrates the induction of apoptosis in HEP 3B and IMR 32 cells after treatment with , , , and .

4,4'-Diaminodiphenyl ether derivatives: synthesis, spectral, optical, thermal characterization and in-vitro cytotoxicity against Hep 3B and IMR 32 human cell lines.

4,4'-Diaminodiphenyl ether was selected as a lead compound to prepare a novel series of bisimine derivatives bearing polyaromatic hydrocarbon substituents and their reduced benzyl forms. The new compounds were structurally characterized by microanalysis, mass, IR, (1)H, (13)C, DEPT-135, HSQC, g-COSY NMR spectroscopy, UV-visible, fluorescence spectrophotometers and by thermogravimetric analysis. The antitumor activity of these derivatives was evaluated in-vitro against Hep 3B and IMR 32 by the MTT assay and the results were compared with cisplatin. Interestingly, some compounds were found extremely active against both the cell lines and proved to be more potent as cytotoxic agents than cisplatin. Morphological evidences suggest the induction of apoptosis and explain the mode of action of these derivatives as antitumor agents.