Synthesis and antibacterial activity of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl)piperazinyl quinolone derivatives

A series of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl) derivatives of piperazinyl quinolones was synthesized and evaluated for antibacterial activity against Gram-positive and Gram-negative microorganisms. Some of these derivatives exhibit high activity against Gram-positive bacteria; Staphylococcus aureus and Staphylococcus epidermidis, comparable or more potent than their parent N-piperazinyl quinolones norfloxacin and ciprofloxacin as reference drugs. The SAR of this series indicates that both the structure of the benzyl unit and the S or SO2 linker dramatically impact antibacterial activity

Cyclooxygenase inhibitors combined with deuterium-enriched water augment cytotoxicity in A549 lung cancer cell line via activation of apoptosis and MAPK pathways

Objective(s): Combination chemotherapy is a rational strategy to increase patient response and tolerability and to decrease adverse effects and drug resistance. Recently, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to be associated with reduction in occurrence of a variety of cancers including lung cancer. On the other hand, growing evidences suggest that deuterium-enriched water (DEW, D2O) and deuterium-depleted water (DDW) play a role both in treatment and prevention of cancers. In the present study, we examined the effects of DEW and DDW in combination with two NSAIDs, celecoxib and indomethacin, on A549 human non-small lung cancer cell to identify novel treatment options. Materials and Methods: The cytotoxicity of celecoxib or indomethacin, alone and in combination with DDW and DEW was determined. The COX-2, MAPK pathway proteins, the anti-apoptotic Bcl2 and pro-apoptotic Bax proteins and caspase-3 activity were studied for cytotoxic combinations.Results: Co-administration of selective and non-selective COX-2 inhibitors with DEW led to a remarkable increase in cytotoxicity and apoptosis of A549 cells. These events were associated with activation of p38 and JNK MAPKs and decreasing pro-survival proteins Bcl-2, COX-2 and ERK1/2. Furthermore, the combination therapy activated caspase-3, and the apoptosis mediator, and disabled poly ADP-ribose polymerase (PARP), the key DNA repair enzyme, by cleaving it.  Conclusion: The combination of DEW with NSAIDs might be effective against lung cancer cells by influence on principal cell signalling pathways, and this has a potential to become a candidate for chemotherapy

Synthesis and antibacterial activity of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl)piperazinyl quinolone derivatives

A series of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl) derivatives of piperazinyl quinolones was synthesized and evaluated for antibacterial activity against Gram-positive and Gram-negative microorganisms. Some of these derivatives exhibit high activity against Gram-positive bacteria; Staphylococcus aureus and Staphylococcus epidermidis, comparable or more potent than their parent N-piperazinyl quinolones norfloxacin and ciprofloxacin as reference drugs. The SAR of this series indicates that both the structure of the benzyl unit and the S or SO2 linker dramatically impact antibacterial activity

Erythromycin B: conformational analysis and antibacterial activity

Erythromycin B, an acid-stable co-metabolite of the important antibiotic erythromycin A, differs from erythromycin A only in the absence of a hydroxyl group at C12, yet it has never been licensed for clinical use. We describe an NMR-based analysis of the conformation of erythromycin B, both free in aqueous solution and when weakly bound to bacterial ribosomes and show that it is conformationally similar to erythromycin A. The antibacterial activity of erythromycin B is shown to be similar to that of erythromycin A, but after acid-treatment, resembling exposure to the stomach, erythromycin B substantially retains antibacterial activity, whereas erythromycin A does not

CCDC 286533: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

The Effect of Clinical Skills Training on Medical Students Clinical Competencies in the Management of Vaginal Delivery

Introduction. Clinical skills training program provides an opportunity for medical students to improve their clinical skills in a simulated setting which is designed and equipped for learning a number of key skills by practicing on manikins and related equipments. The aim of this study was to determine the effect of clinical skills training program on clinical competencies of medical students in the management of vaginal delivery in Tabriz Medical University. Methods. In this quasi-experimental research with one group, pre- and post-test design, 50 medical students were selected randomly and assessed using a valid and reliable questionnaire asking about their clinical competencies in the management of different stages of vaginal delivery and also about their suturing skill. Likert scale was used for determining the level of competency based on self-assessment approach. Data analysis was done by SPSS software using descriptive analysis, paired t-test, ANOVA and Pearson correlation coefficient. Results. A significant increase was observed in the mean score of skills related to pre-delivery stage (from 14±13.65 to 89±10.72), skills needed during performing the delivery (from 18.17±13.3 to 88.95±9.26), and skills needed during the post-delivery stage such as suturing and dressing (from 31.07±16.57 to 85.17±12.78). There was a significant difference between the mean score related to the skills needed before, during and after delivery, before and after education. Conclusion. Practicing in Clinical Skills Center considerably increased perceived self-efficacy of medical students for doing the skills needed for the management of a safe vaginal delivery which in turn could lead to increasing their skills in confronting patients

A Comparison of Case-Control and Case-Only Designs to Investigate Gene-Environment Interactions Using Breast Cancer Data

Background: The traditional methods of studying the gene-environment interactions need a control group. However, the selection of an appropriate control group has been associated with problems. Therefore, new methods, such as case-only design, have been created to study such interactions. The objective of this study was to compare the case-only and case-control designs using data from patients with breast cancer.Methods: The interaction of genetic and environmental factor as well as the ratio of control to population odds ratio was calculated for case-only (300 patients with breast cancer) and case-control (300 cases of breast cancer and 300 matched controls) designs. Results: The confidence intervals and -2log likelihood in all variables in case-only design was smaller than those in the matched case-control design. In case-only design, the standard errors of some variables such as age at menarche, the first delivery at the age of 35 yrs and more or no delivery, the history of having live birth, use of oral contraception pills, breastfeeding history were less than those in the matched case-control design. Conclusion: The findings indicate that the case-only design is an efficient method to investigate the interaction of genetic and environmental factors

Quantitative Structure-Activity Relationship Study on Thiosemicarbazone Derivatives as Antitubercular agents Using Artificial Neural Network and Multiple Linear Regression

Background and purpose: Nonlinear analysis methods for quantitative structure–activity relationship (QSAR) studies better describe molecular behaviors, than linear analysis. Artificial neural networks are mathematical models and algorithms which imitate the information process and learning of human brain. Some S-alkyl derivatives of thiosemicarbazone are shown to be beneficial in prevention and treatment of mycobacterial infections and this study seeks to find out the relationship between structural features and the anti-tuberculosis activity of these compounds. Materials and methods: Multiple linear regression and Bayesian regularized artificial neural network (BRANN) for 47 compounds of thiosemicarbazone derivatives were designed using QSAR approaches. Descriptors were selected from a pool of 343 descriptors by stepwise selection and backward elimination. A three layer Bayesian regularized back-propagation feed-forward network was designed, optimized, and evaluated using MATLAB version R2009a. Results: The best model with 6 descriptors was found using multiple linear regression analysis: Log MIC= 2.592 + (0.067 ± 0.018) PMIX – (0.066 ± 0.017) PMIZ – (1.706 ± 1.600) Qneg – (0.235 ± 0.039) RDF030p + (0.118 ± 0.026) RDF 140u – (0.064 ± 0.021) RDF060p. The best BRANN model was a three-layer network with three nodes in its hidden layer. Conclusion: The BRANN model has a better predictive power than linear models and may better predict the anti-tuberculosis activity of new compounds with similar backbone of thiosemicarbazone moiety