New Benzimidazole-Triazole Derivatives as Topoisomerase I Inhibitors: Design, Synthesis, Anticancer Screening, and Molecular Modeling Studies.

In this study, we designed, synthesized, and evaluated a series of 1,2,4-triazole benzimidazoles for their cytotoxic effects against the A549, C6, and NIH3T3 cell lines. Additionally, these compounds were assessed for their inhibitory activity against DNA topoisomerase I, aiming to develop novel anticancer agents. The synthesized final compounds 4a-h were characterized using 1H NMR, 13C NMR, and HRMS. Among them, compounds 4b and 4h emerged as the most potent agents against the A549 cell line, exhibiting an IC50 value of 7.34 ± 0.21 µM and 4.56 ± 0.18 µM, respectively. These results were compared to standard drugs, doxorubicin (IC50 = 12.420 ± 0.5 µM) and Hoechst 33342 (IC50 = 0.422 ± 0.02 µM). Notably, all tested compounds displayed higher cytotoxicity toward A549 cells than C6 cells. Compounds 4b and 4h demonstrated significant inhibitory activity against topoisomerase I, highlighting their potential as lead compounds in anticancer therapy. Subsequent in silico molecular docking studies were conducted to elucidate the potential binding interactions of compounds 4b and 4h with the target enzyme topoisomerase I. Molecular dynamics studies also assessed and validated the binding affinity and stability. These studies confirmed the promising binding affinity of these compounds, reinforcing their status as lead candidates. According to DFT, compound 4b having the lower energy gap value (ΔE = 3.598 eV) is more chemically reactive than the others, which is consistent with significant inhibitory activity against topoisomerase I. Furthermore, in silico ADME profiles for compounds 4b and 4h were evaluated using SwissADME, providing insights into their pharmacokinetic properties.

Design, synthesis and apoptotic effects of novel benzoxazole compounds.

A series of new benzoxazole-hydrazone and benzoxazole-1,3,4-oxadiazole derivatives have been designed, synthesized and evaluated as cytotoxic agents toward human A549 lung cancer cells. Compounds 3d, 3e, 5b, 5c, 5d and 5e were the most potent compounds with IC50 values of <3.9, 10.33, 11.6, 5.00, <3.9 and 4.5 µg/mL, respectively, which are higher than reference drug cisplatin (IC50 = 19.00 µg/mL). The flow cytometry-based apoptosis detection assay was performed to determine their effects on apoptosis in A549 cells. All tested compounds induced apoptosis in A549 cell line.

Design and Synthesis of New 1,3,4-Oxadiazole - Benzothiazole and Hydrazone Derivatives as Promising Chemotherapeutic Agents.

Looking for new cytotoxic and antimicrobial agents with improved antitumor activity, a series of hydrazide and oxadiazole derivatives were designed and synthesized using 3-methoxyphenol as starting substance. Novel N'-(arylidene)-2-(3-methoxyphenoxy)acetohydrazide derivatives (4a-f)/1-(4-substitutedphenyl)-2-[(5-[(3-methoxyphenoxy)methyl]-1,3,4-oxadiazol-2-yl)thio]ethan-1-one derivatives (6a-f)/N-(6-substitutedbenzothiazol-2-yl)-2-[(5-[(3-methoxyphenoxy)methyl]-1,3,4-oxadiazol-2-yl)thio]acetamide derivatives (7a-e) were obtained and evaluated for their in vitro antimicrobial activity against various gram-positive, gram-negative bacteria and fungi. The antimicrobial activity potential of the compounds against gram-negative bacteria was found to have higher compared to the potential against gram-positive bacteria. Also, compounds were screened for their antiproliferative activity against 2 selected human tumor cell lines, A549 lung, MCF7 breast cancer cell line and mouse embryo fibroblast cell line, NIH/3T3 as healthy cell line. Among the compounds evaluated, compound 7c bearing 1,3,4-oxadiazole ring and 6-methoxy benzothiazole moiety exhibited the highest inhibitory activity against A549 and MCF-7 tumor cell lines in contrary to NIH/3T3 cell line, as desired.

Novel 1-(2-pyrimidin-2-yl)piperazine derivatives as selective monoamine oxidase (MAO)-A inhibitors.

In the present study, a new series of 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-2-oxoethyl 4-substituted piperazine-1-carbodithioate derivatives (2a-n) were synthesized and screened for their monoamine oxidase A and B inhibitory activity. The structures of compounds were elucidated using spectroscopic methods and some physicochemical properties of new compounds were predicted using Molinspiration and MolSoft programs. Compounds 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-2-oxoethyl 4-(4-nitrophenyl)piperazine-1-carbodithioate (2j) and 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-2-oxoethyl 4-benzhydrylpiperazine-1-carbodithioate (2m) exhibited selective MAO-A inhibitory activity with IC50 = 23.10, 24.14 µM, respectively. Some of the biological results were found in accordance with the obtained in silico data based on Lipinski's fule of five.

Synthesis of some novel 2-substituted benzothiazole derivatives containing benzylamine moiety as monoamine oxidase inhibitory agents.

In the present work, 12 new 2-(5-substituted-benzothiazol-2-ylsulfanyl)-N-(substitutedbenzyl)-N-(4-substitutedphenyl) acetamide derivatives (4a-l) was designed and synthesized. The structures of the synthesized compounds were clarified using Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance ((1)H-NMR), carbon-13 nuclear magnetic resonance ((13)C-NMR) and high-resolution mass spectrometry (HRMS) spectral data. Purity of synthesized compounds was checked by high-performance liquid chromatography (HPLC) analyses and purity ratio was found between 96.5-99.9%. The inhibitory activity of the compounds against MAO-A and MAO-B enzymes was evaluated by using in vitro flurometric method in which kynuramine was used as a substrate. Most of the compounds exhibited more selective inhibitory activity towards monoamine oxidase B (MAO-B) than monoamine oxidase A (MAO-A). Compound 4h was determined as the most potent compound against both enzyme types. The MAO-B enzyme kinetic of the compound 4h was studied and nature of MAO-B inhibition, caused by this compound, was investigated. The graphical analysis of steady-state inhibition data indicated that compound 4h is a mixed type inhibitor. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME) properties for the synthesized compounds was also carried out and observed data supported the potential of compound 4h.

Effects of three different irrigating solutions and KTP laser irradiation on apical leakage: an electrochemical study.

OBJECTIVE: The purpose of this study was to evaluate the effect of three different irrigating solutions (17% EDTA, 10% citric acid and 2.5% NaOCl) and KTP laser irradiation on apical leakage using an electrochemical method. MATERIALS AND METHODS: Sixty extracted single-rooted human teeth with mature apices were instrumented up to a size 35 K-file. After using each file and before proceeding to the next, canals were irrigated with 2 ml of 2.5% NaOCl. All teeth were then randomly divided into four groups. In group 1, the root canals were irrigated with a final flush of 17% EDTA. In group 2, the root canals were irrigated with a final flush of 10% citric acid. In group 3, the root canals were irradiated with KTP laser at 1 W, 4.45 J/cm(2). In group 4, the root canals were irrigated with a final flush of 2.5% NaOCl. The root canals were then filled using the cold lateral condensation method. Apical leakage was evaluated using an electrochemical method over a period of 10 days. Data were analysed using Tukey HSD and Friedmann tests with p = 0.05 as the level for statistical significance. RESULTS: The 17% EDTA and 10% citric acid groups had statistically less apical leakage than the 2.5% NaOCl group at days 7, 8, 9 and 10 (p < 0.05); however, no significant differences were found between the tested groups at the other time intervals (p > 0.05). No significant difference was found between the KTP laser group and other groups tested at all time intervals (p > 0.05). CONCLUSION: All groups were unable to eliminate apical leakage. However, final irrigation with 17% EDTA and 10% citric acid following root canal preparation reduced postobturation apical leakage compared with 2.5% NaOCl irrigation. When KTP laser and the other three irrigants were compared, no significant difference was found.

Impact of cognitive impairment on functional outcome in stroke.

The aim of this study was to investigate the effect of the cognitive impairment on functional status in patients with subacute stroke. Fifty-two patients with subacute stroke were included in the study. Mini mental state examination (MMSE) test was used for the evaluation of cognitive status. Patients were separated into two groups according to their cognitive functions. Functional follow-up parameters were activities of daily living (ADL), global recovery and ambulation status. All patients were evaluated on admission to rehabilitation unit, at discharge and 6 months after discharge. Forty-four patients were completed the study. Mean age was 66 and 57 years; disease duration on admission was 4,8 and 3,5 months in the cognitively impaired and normal groups, respectively. Significant improvement was found in terms of functional follow-up parameters in both groups at discharge (P < .05). Functional follow-up parameters did not show statistically significant difference between the groups. But community ambulation rate was higher in cognitively normal group at the sixth month visit. As a result of this study, inpatient rehabilitation was effective both cognitively normal and impaired subacute stroke patients.

Relationship between bone turnover and bone density at the proximal femur in stroke patients.

OBJECTIVE: To investigate the relationship between the rate of bone turnover and bone loss at the proximal femur in stroke patients. METHODS: This study was performed between January 1, 2005 and August 31, 2006 at the Stroke Rehabilitation Unit, Istanbul Physical Medicine and Rehabilitation Training Hospital, Istanbul, Turkey. One hundred six patients who had a stroke for the first time were included in the study. The control group consisted of 33 age- and gender-matched healthy subjects. Bone mineral density (BMD) was measured at the proximal hip region by dual energy X-ray absorptiometry (DXA). Serum osteocalcin (OC) and C telopeptide of type 1 collagen (CTX) levels were measured. Barthel Index (BI) was used for the evaluation of daily activities. Ambulation status of the patients was recorded. RESULTS: Mean age was 65.1 +/- 9.8 years in the patient group and 51% were male. Mean disease duration was 16.9 +/- 9.1 months. Mean BI score was 60.5 +/- 25.8 on admission. Femoral neck BMD values were 0.873 +/- 0.95 g/cm(2) and 0.816 +/- 0.180 g/cm(2) for control subjects and hemiplegic sides of the patient group, respectively. Femur total BMD values were 0.948 +/- 0.119 g/cm(2) and 0.872 +/- 0.187 g/cm(2) for control group and hemiplegic sides of the patients, respectively. Femoral neck and femur total BMD values in the hemiplegic side were lower than those of controls' (P < .05). There was no statistically significant difference between the proximal femur BMD values of the intact and hemiplegic sides. Negative correlation was found between the proximal femur BMD values of both the intact and hemiplegic sides, and serum OC and CTX levels. Bone resorption rate was higher among the patients with stroke; however, bone formation rate was normal in this group. Serum CTX levels showed correlation with ambulation status. Femoral neck BMD values on the intact side were lower in the patient group with disease duration of more than 1 year compared to those with shorter disease duration. CONCLUSION: As a result of this study bone turnover was inversely correlated with bone density at the hip of both hemiplegic and intact sides in stroke patients. Evaluation of bone turnover might be helpful to predict bone loss and to find out the stroke patients with bone loss who can not be decided to begin antiresorptive treatment with bone density measurement.

Evaluation of the clinical efficacy of conservative treatment in the management of carpal tunnel syndrome.

INTRODUCTION: Carpal tunnel syndrome (CTS) is impingement of the median nerve at the wrist. The aim of this study was to compare the effectiveness of tendon and nerve gliding exercises with standard conservative treatment (SCT), which consists of splinting and local steroid injections, in the treatment of CTS. METHODS: This study was a prospective, randomized, single-blind trial. Patients were randomized into three groups: treatment with SCT (Group 1); SCT and tendon and nerve gliding exercises (Group 2); tendon and nerve gliding exercises only (Group 3). A symptom total point score was obtained from five symptoms: hand pain, tingling, numbness, nocturnal numbness, and interrupted sleep. The functional status of the hand was determined by assessing seven daily living activities: writing, buttoning clothes, gripping a telephone receiver, opening jars, doing housework, carrying grocery bags, and bathing. Standard physical examinations (Tinel's test, Phalen's test, reverse Phalen's test, and the compression test) were also performed. RESULTS: A total of 111 patients who were diagnosed with intermediate-stage CTS were included in the study. At the end of treatment, significant improvements in symptoms and functionality were detected in all groups. However, the recovery of patients in Groups 1 (n=41) and 2 (n=35) were found to be significantly greater than that of patients in Group 3 (n=35; P<0.001). Patient satisfaction was investigated a mean of 11 months after treatment. Percentages of asymptomatic patients in Group 1 and Group 2 were significantly higher than in Group 3 (P=0.02 and P=0.04, respectively). CONCLUSION: In the intermediate stage of CTS, SCT was an effective treatment to improve symptoms and functional status. Tendon and nerve gliding exercises alone were inferior to either SCT alone or SCT in combination with gliding exercises.

Copper(II)-8-hydroxquinoline coprecipitation system for preconcentration and separation of cobalt(II) and manganese(II) in real samples.

A separation-preconcentration procedure based on the coprecipitation of cobalt(II) and manganese(II) ions with copper(II)-8-hydroxquinoline system has been developed. The analytical parameters including pH, amount of copper(II) as carrier element, amount of 8-hydroxquinoline, sample volume, etc., was investigated for the quantitative recoveries of Co(II) and Mn(II). No interferic effects were observed from the concomitant ions which are present in real samples. The detection limits for analyte ions by three sigma criteria were 0.86microgL(-1) for cobalt and 0.98microgL(-1) for manganese. The validation of the presented preconcentration procedure was performed by the analysis of NIST SRM 2711 Montana soil and GBW 07605 Tea certified reference materials. The procedure presented was applied to the analyte contents of real samples including natural waters and some food samples with successfully analytical results.