Synthesis, in vitro antifungal evaluation and in silico study of 3-azolyl-4-chromanone phenylhydrazones

BACKGROUND: The currently available antifungal drugs suffer from toxicity, greatest potential drug interactions with other drugs, insufficient pharmacokinetics properties, and development of resistance. Thus, development of new antifungal agents with optimum pharmacokinetics and less toxicity is urgent task. In the search for new azole antifungals, we have been previously described azolylchromanone oxime ethers as rigid analogs of oxiconazole. In continuation of our work, we incorporated phenylhydrazone moiety instead of oxime ether fragment in azolylchromanone derivatives. METHODS: The 3-azolyl-4-chromanone phenylhydrazones were synthesized via ring closure of 2-azolyl-2'-hydroxyacetophenones and subsequent reaction with phenylhydrazine. The biological activity of title compounds was evaluated against different pathogenic fungi including Candida albicans, Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum. Docking study, in silico toxicity risks and drug-likeness predictions were used to better define of title compounds as antifungal agents. RESULTS: The in vitro antifungal activity of compounds based on MIC values revealed that all compounds showed good antifungal activity against C. albicans, S. cerevisiae and M. gypseum at concentrations less than 16 μg/mL. Among the test compounds, 2-methyl-3-imidazolyl derivative 3b showed the highest values of drug-likeness and drug-score. CONCLUSION: The 3-azolyl-4-chromanone phenylhydrazones considered as analogs of 3-azolyl-4-chromanone oxime ethers basically designed as antifungal agents. The antifungal activity of title compounds was comparable to that of standard drug fluconazole. The drug-likeness data of synthesized compounds make them promising leads for future development of antifungal agents

Narcissism, self-esteem, communication apprehension, and need for affiliation: difference between social networking site users and non-users

Nowadays, people are increasingly using social networking sites to initiate and maintain friendships, obtain social support and gather data. Personal traits could potentially drive people to join social networking sites as well as indulge in other related behaviors. This study aims to examine whether people with the need for affiliation, narcissism, self- esteem and communication apprehension are more likely to join social networking sites. Data for the current study were collected using convenience sampling; the sample consisted of undergraduate students studying at three private universities in Tehran, Iran. We used IBM SPSS 20 to run logistic regression statistics to test the research hypotheses developed for this study based on the responses from 284 respondents. The results of this study reveal that self-esteem, communication apprehension and the need for affiliation are significant predictors for social networking site usage while narcissism is not

Correlation of immunostaining findings with demographic data and variables of Oxford classification in IgA nephropathy

Background: Oxford classification for IgA nephropathy (IgAN) did not include pattern of immunostaining in the analysis. Objective: The aim of this study is to determine the potential correlation between the immunostaining data and morphologic variables of Oxford classification (MEST) and various clinical and demographic data of patients with IgAN. Patients and Methods: The pathologic diagnosis of IgAN requires the demonstration of IgA-dominant mesangial or mesangio-capillary immune deposits through immunofluorescence (IF) microscopy. The immune deposits were semiquantitatively assessed as 0 to 3+ positive bright. These were correlated with various clinical, demographic and histological variables of Oxford classification. Results: A total of 114 biopsies were enrolled to the study (70.2 were male). Mean age of the patients was 37.7 ± 13.6 years. This study showed that, only C3 deposits had a significant correlation with serum creatinine. Other antibodies (IgA, IgM and IgG) had no significant association with serum creatinine. This study also showed that IgA deposition score had significant positive association with endocapillary proliferation (E) and segmental glomerulosclerosis (S) variables of Oxford classification. Moreover, IgM deposition score had positive association with S variable. There was no significant association of IgG deposition score with four morphologic variables of Oxford classification. There was significant association of C3 deposition score with S and E variables too. Conclusions: The significant relationships of IgA and C3 deposits with some of the Oxford variables need more attention. We propose to further investigate this aspect of IgAN disease. © 2013, Society of Diabetic Nephropathy Prevention. All rights reserved

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

Development and Validation of an HPLC Method for the Analysis of Sirolimus in Drug Products

Purpose: The aim of this study was to develop a simple, rapid and sensitive reverse phase high performance liquid chromatography (RP-HPLC) method for quantification of sirolimus (SRL) in pharmaceutical dosage forms. Methods: The chromatographic system employs isocratic elution using a Knauer- C18, 5 mm, 4.6 × 150 mm. Mobile phase consisting of acetonitril and ammonium acetate buffer set at flow rate 1.5 ml/min. The analyte was detected and quantified at 278nm using ultraviolet detector. The method was validated as per ICH guidelines. Results: The standard curve was found to have a linear relationship (r2 > 0.99) over the analytical range of 125–2000ng/ml. For all quality control (QC) standards in intraday and interday assay, accuracy and precision range were -0.96 to 6.30 and 0.86 to 13.74 respectively, demonstrating the precision and accuracy over the analytical range. Samples were stable during preparation and analysis procedure. Conclusion: Therefore the rapid and sensitive developed method can be used for the routine analysis of sirolimus such as dissolution and stability assays of pre- and post-marketed dosage forms

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