Synthesis of novel tetra-substituted benzimidazole compounds containing certain heterostructures with antioxidant and anti-urease activities

A new series of 5,6-dimethyl-2-phenyl-1H-benzimidazole derivatives was synthesized. The antioxidant activities of the synthesized compounds were determined according to the cupric reducing antioxidant capacity (CUPRAC), ABTS, and DPPH assays. Many of the target compounds showed good antioxidant activity. Among these compounds, it has been determined that the carbothioamide and 1,2,4-triazole derivatives had a very good antioxidant capacity. Also, all compounds were screened for in vitro inhibitory activity against Jack bean urease. Among the synthesized molecules, the starting compound, acetate, and acetohydrazide derivatives (with IC₅₀ values 12.02, 11.40, and 8.04 μg/mL, respectively) had a higher inhibitory effect on urease and exhibited a lower IC₅₀ values than acetohydroxamic acid (IC₅₀: 20.50 μg/mL) and thiourea (IC₅₀: 14.04 μg/mL) as a reference inhibitors.     

Design,Synthesis, and Molecular Docking of Paracyclophanyl-Thiazole Hybrids as Novel CDK1 Inhibitors and Apoptosis Inducing Anti-Melanoma Agents

Three new series of paracyclophanyl-dihydronaphtho[2,3-d]thiazoles and paracyclophanyl-thiazolium bromides were designed, synthesized, and characterized by their spectroscopic data, along with X-ray analysis. One-dose assay results of anticancer activity indicated that 3a–e had the highest ability to inhibit the proliferation of different cancer cell lines. Moreover, the hybrids 3c–e were selected for five-dose analyses to demonstrate a broad spectrum of antitumor activity without apparent selectivity. Interestingly, series I compounds (Z)-N-substituted-4,9-dihydronaphtho[2,3-d]thiazol-3(2H)-yl)-4′-[2.2]paracyclophanylamide) that are carrying 1,4-dihydronaphthoquinone were more active as antiproliferative agents than their naphthalene-containing congeners (series II: substituted 2-(4′-[2.2]paracyclophanyl)hydrazinyl)-4-(naphth-2-yl)-thiazol-3-ium bromide hybrids) and (series III: 3-(4′-[2.2]paracyclophanyl)amido-2-(cyclopropylamino)-4-(naphth-2-yl)thiazol-3-ium bromide) toward the SK-MEL-5 melanoma cell line. Further antiproliferation investigations of 3c and 3e on the healthy, normal unaffected SK-MEL-5 cell line indicated their relative safety. Compound 3c showed an inhibition of eight isoforms of cyclin-dependent kinases (CDK); however, it exhibited the lowest IC₅₀ of 54.8 nM on CDK1 in comparison to Dinaciclib as a reference. Additionally, compound 3c revealed a remarkable downregulation of phospho-Tyr15 with a level (7.45 pg/mL) close to the reference. 3c mainly showed cell cycle arrest in the pre-G1 and G2/M phases upon analysis of the SK-MEL-5 cell line. The sequential caspase-3 assay for 3c indicated a remarkable overexpression level. Finally, a molecular docking study was adopted to elucidate the binding mode and interactions of the target compounds with CDK1.     

Surface characterization and radical decay studies of oxygen plasma‐treated PMMA films

Polymethylmethacrylate (PMMA) films were modified by RF oxygen plasma with various powers applied for different periods, and the effects of these parameters on the surface properties such as hydrophilicity, surface free energy (SFE), chemistry, and topography were investigated by water contact angle, goniometer, X‐ray photoelectron spectroscopy (XPS), and atomic force microscopy, and the types of the created free radicals and their decay were detected by electron spin resonance spectroscopy (ESR). SFE and contact angle results varied depending on the plasma parameters. Oxygen plasma treatment (100 W–30 min) enhanced the hydrophilicity of PMMA surface as shown by decreasing the water contact angle from 70° to 26°. XPS analysis showed the change in the amounts of the present functionalities as well as formation of new groups as free carbonyl and carbonate groups. The roughness of the surface increased considerably from ~2 nm to ~75 nm after 100 W–30 min oxygen plasma treatment. ESR analysis indicated the introduction of peroxy radicals by oxygen plasma treatment, and the intensity of the radicals increased with increasing the applied power. Significant decrease in radical concentration was observed especially for the samples treated with higher powers when the samples were kept under the atmospheric conditions. As a conclusion, RF plasma, causes changes in the chemical and physical properties of the materials depending on the applied parameters, and can be used for the creation of specific groups or radicals to link or immobilize active molecules onto the surface of a material. Copyright © 2012 John Wiley & Sons, Ltd.     

6‐(3,4‐Di­fluoro­benzoyl)‐3‐[2‐(4‐pyridyl)­ethyl]‐1,3‐benzo­thia­zol‐2(3H)‐one

A new type of benzo­thia­zolinone derivative with potential pharmacological activity, viz. 6‐(3,4‐di­fluoro­benzoyl)‐3‐[2‐(4‐pyridyl)­ethyl]‐1,3‐benzo­thia­zol‐2(3H)‐one, C₂₁H₁₄F₂N₂O₂S, has been prepared and studied by NMR, IR and single‐crystal X‐ray diffraction techniques. The mol­ecule is not planar, the pyridine and di­fluoro­benzene moieties being located above and below the benzo­thia­zole ring system. The carbonyl O atoms are involved in an intramolecular hydrogen‐bond‐type interaction.     

A generalization of the Weierstrass semigroup

The Weierstrass semigroup H(P) is well known and has been studied. Recently there has been a renewed interest in these semigroups because of applications in coding theory. Generalizations of the Weierstrass semigroup H(P) to n-tuples P₁,…,P_n have been made and studied. We will state and study another possible generalization.     

Molecular structure of 2-methylamino-5-[(5-methyl-2-benzoxazolinone-3-yl)methyl]-1,3,4-thiadiazole dihydrophosphate: a combined X-ray crystallographic and ab initio study

Crystal structure of the compound entitled 2-methylamino-5-[(5-methyl-2-benzoxazolinone-3-yl)methyl]-1,3,4-thiadiazole dihydrophosphate is determined using X-ray analysis and compared with the structure obtained from semiempirical and RHF methods at various levels of theory. RHF/6-31G(d) calculations offer the best conformity with X-ray results for bond lengths and bond angles. Moreover, at the result of the comparison of various combinations of basis sets and methods, it appears that there is not much gain in accuracy by using sophisticated methods.     

New Pyrimidine‐2‐thiones from Reactions of Amidrazonethiols with 2‐Amino‐1,1,2‐ethenetricarbonitrile and Investigation of Their Antitumor Activity

Reactions of thiosemicarbazones with 2‐amino‐1,1,2‐ethenetricarbonitrile were reported. The reaction occurred in the amidrazonyl site, and new pyrimidine‐2‐thiones were obtained. The reaction mechanism was discussed. The structure of products was elucidated by MS, IR, and NMR spectra together with elemental analyses. The antitumor activity was evaluated against one tumor cell line. Using a standard MTT assay, the effect of the samples on the growth of HepG2 cells was investigated. Half of these compounds showed no cytotoxic effect on HepG2 cells, while the others result in decreasing in the HepG2 cell viability.     

Amination of Malononitrile Dimer to Amidines: Synthesis of 6‐aminopyrimidines

Reactions of amidines with malononitrile dimer in DMF and catalyzed with piperidine are reported. The reaction occurred via amination process followed by cyclization to give racemic 6‐aminopyrimidine compounds. The reaction mechanism was discussed. The structure of products was elucidated by mass spectrometry, IR and NMR spectra together with elemental analyses.     

Determination of the health hazards due to background radiation sources in the city of Adapazari, Northwestern Turkey

Human body is exposed to ionising radiations both internally and externally by mainly high-energy cosmic ray particles incident on the earth's atmosphere and radioactive nuclides that originated in the earth's crust. The main objective of this study is to assess the health hazards due to environmental radiation sources in the city of Adapazari, one of the most important industrial cities of the country, Northwestern Turkey. For this purpose, natural radiation sources, external terrestrial radiations, cosmic radiations, and inhalation exposures have been investigated. The annual average external terrestrial radiation doses were determined as 0.08 and 0.35 mSv at outdoor and indoor atmospheres, respectively. The annual average cosmic radiation doses were found to be 0.08 and 0.05 mSv for directly ionising photon components and neutron components, respectively. The annual average inhalation exposure doses due to radon and thoron were obtained as 1.42 and 0.19 mSv, respectively, in the region. The annual average effective dose due to natural radiation sources was determined as a total of 2.35 mSv with the predetermined ingestion radiation dose. The lifetime cancer risk due to the background ionising radiations has been determined as 0.9×10(-2) for the residents of the Adapazari city, with the average lifespan of 70 years. The results of the effective doses due to background radiation sources in the region and the worldwide averages were discussed.