Novel Thiazolidinone-Azole Hybrids: Design, Synthesis and Antimycobacterial Activity Studies

Abstract To develop novel antimycobacterial agents, a new series of thiazolidinone-azole hybrids 4a-b, 5a-b and 6-13 were designed and synthesized. Thiazolidin-4-ones (4a-b and 5a-b) were obtained by the reaction of Schiff bases and hydrazones (2a-b and 3a-b) with mercaptoacetic acid. 5-Benzylidene derivatives (6-13) were gained by treatment of 5a-b with appropriate benzaldehydes according to Knoevenagel condensation. To evaluate their structures 1 H NMR, IR, mass spectrometry and elemental analysis data were used. The target compounds were screened for their antimycobacterial activity against M. tuberculosis H37Rv strain using the microplate alamar blue assay method. Among them, 6, 10 and 12 (MIC: 14.27-14.74 μM) were found as most active compounds in the series. It was seen that both phenylamino and benzylidene substitutions on thiazolidin-4-one ring caused an improvement in the antimycobacterial activity

BRG1 co-localizes with DNA replication factors and is required for efficient replication fork progression

For DNA replication to occur, chromatin must be remodeled. Yet, we know very little about which proteins alter nucleosome occupancy at origins and replication forks and for what aspects of replication they are required. Here, we demonstrate that the BRG1 catalytic subunit of mammalian SWI/SNF-related complexes co-localizes with origin recognition complexes, GINS complexes, and proliferating cell nuclear antigen at sites of DNA replication on extended chromatin fibers. The specific pattern of BRG1 occupancy suggests it does not participate in origin selection but is involved in the firing of origins and the process of replication elongation. This latter function is confirmed by the fact that Brg1 mutant mouse embryos and RNAi knockdown cells exhibit a 50% reduction in replication fork progression rates, which is associated with decreased cell proliferation. This novel function of BRG1 is consistent with its requirement during embryogenesis and its role as a tumor suppressor to maintain genome stability and prevent cancer

ICAR: endoscopic skull‐base surgery

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Isoquinoline alkaloids isolated from Glaucium corniculatum var. corniculatum and Glaucium grandiflorum subsp. refractum var. torquatum with bioactivity studies

AbstractContext The genus Glaucium Mill., one of the important Papaveraceae family plants, is rich in isoquinoline alkaloids and distributed worldwide.Objective Isolation and identification of bioactive alkaloids from Glaucium grandiflorum Boiss. & Huet. subsp. refractum (Nabelek) Mory var. torquatum (Cullen) Mory and G. corniculatum (L.) Rudolph var. corniculatum (Aslan 2012), and investigation of their antioxidant and anticholinesterase activities.Materials and methods The aerial parts of each plant were dried, powdered, and percolated with methanol, then each extract was fractionated between 50% aqueous acetic acid and petroleum. Their aqueous acidic layer was adjusted to pH 7–8 with NH4OH and extracted with chloroform, the extract was subjected to CC separation and isolation. Structures of the isolated alkaloids were elucidated by 1D and 2D-NMR and mass spectral analyses. The alkaloid extracts and their pure alkaloids were tested for anti-cholinesterase (AChE and BuChE) and antioxidant (ABTS, CUPRAC, β-carotene linoleic acid tests) activities in vitro.Results Methanol extracts of Glaucium grandiflorum subsp. refractum var. torquatum and G. corniculatum var. corniculatum afforded a novel compound glauciumoline and seven known isoquinoline alkaloids three of which have an aporphine-type and the other five have a protopine-type skeleton. Among them, trans-protopinium (7) and cis-protopinium (8) were isolated from a Glaucium species for the first time. Tertiary amine extracts (TAEs) of both plants showed very strong acetylcholinesterase inhibitory activity. The TAE of the plants also showed strong antioxidant activity while the isolated alkaloids showed no meaningful activity in the anticholinesterase and antioxidant tests.Discussion and conclusions Glaucium species are considered promising therapeutic agents in the treatment of Alzheimer’s disease

A Comparative Study on Monomer Elution and Cytotoxicity of Different Adhesive Restoration Materials

This study evaluated monomer release and cytotoxicity of different adhesive restoration materials used for dental restorations. The extracts (1, 2, and 7days) of three types of adhesive dental restoration materials, [Quixfill (QF), Silorane Restorative (SR), and Ketac N 100 Restorative (KR)], and the adhesive resins, [XP Bond (XP), Silorane Primer (SP), Ketac N 100 Primer (KP), and Silorane Bond (SB)] were analyzed using high performance liquid chromatography/mass spectrometry (HPLC-MS). The cytotoxicity levels were determined at different time points (24, 48, and 72h) of cell culture using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. All adhesive resin materials showed monomer release at varying amounts with the highest release after 7days. The lowest amount of release was observed in QF and the highest with KP. Bis-Phenol A (BPA) was not detected in SP and KR that contain bisphenol-A diglycidyl ether dimethacrylate (bis-GMA). Decamethylpenthasiloxane (D5) was not eluted from SR. Except for SR and QF, all other adhesive restoration materials showed different degrees of toxicity along with different monomer release kinetics. The correlation between the monomer release and cytotoxicity of the materials indicated that the cytotoxicity of the materials increased with the monomer release (Spearman's rho correlation coefficient - r). The correlation after 48h was statistically significant (r=-0.342, p=0.017).Wo