Insight into eukaryotic topoisomerase II-inhibiting fused heterocyclic compounds in human cancer cell lines by molecular docking.

Etoposide is effective as an anti-tumour drug by inhibiting eukaryotic DNA topoisomerase II via establishing a covalent complex with DNA. Unfortunately, its wide therapeutic application is often hindered by multidrug resistance (MDR), low water solubility and toxicity. In our previous study, new derivatives of benzoxazoles, benzimidazoles and related fused heterocyclic compounds, which exhibited significant eukaryotic DNA topoisomerase II inhibitory activity, were synthesized and exhibited better inhibitory activity compared with the drug etoposide itself. To expose the binding interactions between the eukaryotic topoisomerase II and the active heterocyclic compounds, docking studies were performed, using the software Discovery Studio 2.1, based on the crystal structure of the Topo IIA-bound G-segment DNA (PDB ID: 2RGR). The research was conducted on a selected set of 31 fused heterocyclic compounds with variation in structure and activity. The structural analyses indicate coordinate and hydrogen bonding interactions, van der Waals interactions and hydrophobic interactions between ligands and the protein, as Topo IIA-bound G-segment DNA are responsible for the preference of inhibition and potency. Collectively, the results demonstrate that the compounds 1a, 1c, 3b, 3c, 3e and 4a are significant anti-tumour drug candidates that should be further studied.

Synthesis, antimicrobial activity and QSAR studies of 2,5-disubstituted benzoxazoles.

In this study, a new series of 2,5-disubstituted benzoxazoles was synthesized and their structures were elucidated by elemental analysis, MASS, (1)H-NMR, (13)C-NMR and IR spectral data. Newly and previously synthesized 2,5-disubstituted benzoxazole derivatives were evaluated for antibacterial and antifungal activity against standard strains and their drug-resistant isolates. Microbiological results showed that the compounds presented a large spectrum of activity having MIC values of 250-7.8 microg mL(-1) against the tested microorganisms. Among the newly synthesized derivatives 3-22, compound 11 was the most active against Candida krusei out of all; however, it was one dilution less potent than standard drug fluconazole. In addition, all the new and previous compounds were more active than standard drugs ampicillin trihydrate and rifampicin against Pseudomonas aeruginosa and its gentamicin-resistant isolate. The 2D-QSAR (Quantitative Structure-Activity Relationship) analysis of a set of newly and previously synthesized benzoxazoles tested for growth inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) was also performed by using multivariable regression analysis. The activity contributions for substituent effects of these compounds were determined from the correlation equation for predictions of the lead optimization.

QSAR and pharmacophore analysis on amides against drug-resistant S. aureus.

Considering the worth of developing new antibacterial agents against drug-resistant Stapylococcus aureus, the present study explores the structure-activity relationships analysis of N-(2-hydroxy-4(or 5)-nitro/aminophenyl)benzamide and phenylacetamide derivatives using classical QSAR and 3D-common-feature pharmacophore hypothese approaches. QSAR analysis revealed that the compounds possessing a methylene group between the phenyl and the carboxyamido moiety played a role for decreasing the activity. On the other side, substituent effects on position R1 was found important for the activity and holding a substituent possessing a minimum width property on this position like as alkyl groups enhanced the activity. Moreover, substituting position R3 with a group enhancing the electron-donor capability of the phenolic ring system increased the potency. 3D-common-feature pharmacophore approach considered that the conformational properties of the compounds were important for the activity against drug-resistant S. aureus and compounds possessing a benzamide moiety rather than phenylacetamide structure increased the activity. Furthermore, holding NO2 and OH groups on the phenyl ring attached to the benzamide moiety was important for improving the potency against drug-resistant S. aureus.

Carotid artery stenosis: reproducibility of automated 3D CT angiography analysis method.

The aim of this study was to assess the reproducibility and anatomical accuracy of automated 3D CT angiography analysis software in the evaluation of carotid artery stenosis with reference to rotational DSA (rDSA). Seventy-two vessels in 36 patients with symptomatic carotid stenosis were evaluated by 3D CT angiography and conventional DSA (cDSA). Thirty-one patients also underwent rotational 3D DSA (rDSA). Multislice CT was performed with bolus tracking and slice thickness of 1.5 mm (1-mm collimation, table feed 5 mm/s) and reconstruction interval of 1.0 mm. Two observers independently performed the stenosis measurements on 3D CTA and on MPR rDSA according to the NASCET criteria. The first measurements on CTA utilized an analysis program with automatic stenosis recognition and quantitation. In the subsequent measurements, manual corrections were applied when necessary. Interfering factors for stenosis quantitation, such as calcifications, ulcerations, and adjacent vessels, were registered. Intraobserver and interobserver correlation for CTA were 0.89 and 0.90, respectively (p<0.001). The interobserver correlation between two observers for MPR rDSA was 0.90 (p<0.001). The intertechnique correlation between CTA and rDSA was 0.69 (p<0.001) using automated measurements but increased to 0.81 (p<0.001) with the manually corrected measurements. Automated stenosis recognition achieved a markedly poorer correlation with MPR rDSA in carotids with interfering factors than those in cases where there were no such factors. Automated 3D CT angiography analysis methods are highly reproducible. Manually corrected measurements facilitated avoidance of the interfering factors, such as ulcerations, calcifications, and adjacent vessels, and thus increased anatomical accuracy of arterial delineation by automated CT angiography with reference to MPR rDSA.

Cognition in 4-11 year old children in Turkey.

OBJECTIVES: The purpose of this study was to determine the relationship among age, sex and academic performance with cognitive ability on healthy age groups. METHODS: The subjects were 71 children, aged 4-11 years (x = 7.11). The children were divided into four age groups: 22 of the 71 children were at kindergarten and 49 children were in primary education. Thirty nine children were girls and 32 were boys. Twenty six children had good academic achievement and 23 did not. Each child was tested on the LOTCA battery by the Occupational Therapy Unit of Hacettepe University School of Physical Therapy and Rehabilitation. In this study, seven subtests were used from LOTCA (Loewenstein Occupational Therapy Cognitive Assessment). These are orientation for place, orientation for time, overlapping figures, praxis, reproduction of a two dimensional model, drawing a clock, and categorization. RESULTS: Statistical analysis of the relationships demographic variables, academic achievement and performance on the battery revealed that age was significant, sex was insignificant and academic achievement was significant when correlated with cognitive abilities. CONCLUSIONS: The results suggest that cognitive abilities tested show some differences. For this reason, in the school or other educational settings, children who have low academic achievement should be assessed also for cognitive abilities and then provided with occupational therapy.

The assessment of Bruininks-Oseretsky test of motor proficiency in children.

OBJECTIVE: The primary objective is to research the relationship between motor abilities and demographic characteristics such as age and sex, in healthy children aged 4-11 years. METHODS: One hundred and twenty children in kindergarten (n = 30) and primary school (n = 90) were included in the study and evaluated by the Occupational Therapy Unit. All children were divided into four groups according to age, 4-5, 6-7, 8-9 and 10-11 years. The primary school children were classified according to academic learning, being successful or unsuccessful. In this study, Bruininks-Oseretsky test of motor proficiency was used to assess the gross motor skills and fine motor skills. These tests are running speed and agility (subtest 1/item 1), balance/walking forward heel-to-toe on walking line (subtest 2/item 6), bilateral coordination/tapping-foot and finger on same side synchronized (subtest 3/item 2), strength/standing broad jump (subtest 4/item 1), response speed (subtest 6/item 1), visual motor control/cutting out a circle with preferred hand (subtest 7/item 1), upper-limb speed and dexterity/pacing pennies in two boxes with both hands (subtest 8/item 2). RESULTS: When the children were classified according to sex, there were significant differences in subtests 6 and 7. According to academic learning, there were significant differences in subtests 2 and 8. When the results were evaluated due to age, important differences were found in subtests 1, 2, 4 and 8. CONCLUSION: It was seen that gross and fine motor skills in early childhood showed variety between age, sex and academic learning. The scores of motor abilities were better in successful children than unsuccessful children. The outcome of this study revealed that the Bruininks-Oseretsky test can be useful to investigate unexplored aspects of motor development.