Synthesis, characterization, molecular modeling, and potential antimicrobial and anticancer activities of novel 2-aminoisoindoline-1,3-dione derivatives.

In an effort to establish new drug candidates with improved antimicrobial and anticancer activities, we report here synthesis, molecular modeling, and in vitro biological evaluation of novel substituted N-amino phthalamide derivatives (3a-b, 4a-b, 5a-j, and 6). Structures of the newly synthesized compounds were described by IR, (1)H &(13)CNMR and LC-MS spectral data. The novel compounds were evaluated for their antibacterial activity against four types of Gm+ve and two for Gm-ve types, and antifungal activity against three fungi microorganisms by well diffusion method. Of these novel compounds, Schiff bases showed mostly promising antibacterial activity compared to reference drugs. A successful step was done for explanation of their mode of action through molecular docking of most active molecules at DNA gyrase B enzyme and further were biologically tested. Moreover, the antiproliferative activity was tested against two human carcinoma cell lines (Human colon carcinoma (HCT-116) and human breast adenocarcinoma (MCF-7)) showing promising anticancer activity compared to doxorubicin drug. The data from structure-activity relationship (SAR) analysis revealed that the lypophilic properties of these compounds might be essential parameter for their activity and suggest that 2-amino phthalamide scaffold derivatives 5g and 5h exhibited good antimicrobial and anticancer activities and might used as leads for further optimization.

Spatiotemporal PFQNM visualization of the effect of suicide dendriplexes on dividing HeLa cells.

Suicide gene delivery is significant in cancer therapy but has not been fully investigated on a cellular scale. Here, Peak Force Quantitative Nanomechanical atomic force microscopy (PFQNM-AFM) was applied to visualize the effect of herpes simplex virus thymidine kinase dendriplexes (G4AcFaHSTK) on the morphological and nanomechanical properties of individual live and dividing HeLa cells. Cells were then exposed to G4AcFaHSTK, followed by ganciclovir, and directly imaged by real-time PFQNM-AFM. Cell membrane liquefaction, cytoplasmic shrinkage, and cytoskeleton structure loss were observed during cell division. The average Young's modulus of the nuclear region increased with time as the cell continued from metaphase (6.29 kPa) to telophase (13.6 kPa) and then decreased (2.25 kPa) upon apoptosis. In contrast, cells exposed to either ganciclovir or G4AcFaHSTK alone have no changes. Thus, understanding the real-time effects of suicide dendriplexes on the cytoskeletal and nanomechanical behaviors of cancer cells may provide new methods for cancer treatment.

Knowledge, awareness, and attitudes toward antibiotic use and antimicrobial resistance among Saudi population.

Background Inappropriate use of antibiotics is a public health problem of great concern. Objective To evaluate knowledge of antibiotics, race, gender and age as independent risk factors for self-medication. Setting Residents and population from different regions of Saudi Arabia. Methods We conducted a cross sectional survey study among residents. Data were collected between June 2014 to May, 2015 from 1310 participants and data were recorded anonymously. The questionnaire was randomly distributed by interview of participants and included sociodemographic characteristics, antibiotics knowledge, attitudes and behavior with respect to antibiotics usage. Main outcome measure Population aggregate scores on questions and data were analyzed using univariate logistic regression to evaluate the influence of variables on self-prescription of antibiotics. Results The response rate was 87.7 %. A cumulative 63.6 % of participants reported to have purchased antibiotics without a prescription from pharmacies; 71.1 % reported that they did not finish the antibiotic course as they felt better. The availability of antibiotics without prescription was found to be positively associated with self-medication (OR 0.238, 95 % CI 0.17-0.33). Of those who used prescribed or non-prescribed antibiotics, 44.7 % reported that they kept left-over antibiotics from the incomplete course of treatment for future need. Interestingly, 62 % of respondents who used drugs without prescription agreed with the statement that antibiotics should be access-controlled prescribed by a physician. We also found significant association between storage, knowledge/attitudes and education. Conclusions The overall level of awareness on antibiotics use among residents in Saudi Arabia is low. This mandates public health awareness intervention programs to be implemented on the use of antibiotics.

In vitro susceptibility of Cryptococcus neoformans clinical isolates from Egypt to seven antifungal drugs.

The in vitro susceptibility of 29 clinical isolates of Cryptococcus neoformans to fluconazole, miconazole, itraconazole, ketoconazole, flucytosine, nystatin and amphotericin B was tested by broth and colorimetric microdilution methods. Most of the isolates showed uniform patterns of susceptibility to the used antifungal agents. Only three isolates exhibited resistance [fourfold or greater rise in the minimum inhibitory concentrations (MICs)] to the tested antifungal drugs. The MIC50 and MIC90 were 0.5-8 mg l(-1) for 5-flucytosine, 0.2-8.25 mg l(-1) for nystatin, 0.5-16 mg l(-1) for fluconazole and 0.2-12.5 mg l(-1) for miconazole. However, MIC50 and MIC90 were in narrow range for the clinical yeast isolates in both methods used and showed 0.5-1 mg l(-1) for amphotericin B and 0.016-0.25 mg l(-1) for both ketoconazole and itraconazole. The combination of fluconazole plus flucytosine showed greater synergistic and fungicidal activity compared with that of fluconazole plus amphotericin B or the use of individual drugs.

Inhibition of Listeria monocytogenes LMG10470 by plantaricin UG1 in vitro and in beef meat.

The inhibition of Listeria monocytogenes LMG 10470 occurred due to plantaricin UG1, but not to lactic acid produced by Lactobacillus plantarum UG1 or its negatie variant (BAC). Partially purified plantaricin UG1 had a higher antilisterial activity in vitro and in meat than Lactobacillus plantarum UG1 culture. Plantaricin UG1 activity was higher in brain heart infusion (BHI) broth than in minced meat. The inhibitory effect of plantaricin UG1 against L. monocytogenes LMG10470 was dependent on its concentration. The 22,880 AU/mL appeared to be an ideal meat preservative in this experiment.