Evaluation of antibacterial, cytotoxicity, and apoptosis activity of novel chromene-sulfonamide hybrids synthesized under solvent-free conditions and 3D-QSAR modeling studies.

In this study, eleven novel chromene sulfonamide hybrids were synthesized by a convenient method in accordance with green chemistry. At first, chromene derivatives (1-9a) were prepared through the multi-component reaction between aryl aldehydes, malononitrile, and 3-aminophenol. Then, synthesized chromenes were reacted with appropriate sulfonyl chlorides by grinding method to give the corresponding chromene sulfonamide hybrids (1-11b). Synthesized hybrids were obtained in good to high yield and characterized by IR, 1HNMR, 13CNMR, CHN and melting point techniques. In addition, the broth microdilution assay was used to determine the minimal inhibitory concentration of newly synthesized chromene-sulfonamide hybrids. The MTT test was used to determine the cytotoxicity and apoptotic activity of the newly synthesized compounds against fibroblast L929 cells. The 3D­QSAR analysis confirmed the experimental assays, demonstrating that our predictive model is useful for developing new antibacterial inhibitors. Consequently, molecular docking studies were performed to validate the findings of the 3D-QSAR analysis, confirming the potential binding interactions of the synthesized chromene-sulfonamide hybrids with the target enzymes. Molecular docking studies were employed to support the 3D-QSAR predictions, providing insights into the binding interactions between the newly synthesized chromene-sulfonamide hybrids and their target bacterial enzymes, thereby reinforcing the potential efficacy of these compounds as antibacterial agents. Also, some of the experimental outcomes supported or conflicted with the pharmacokinetic prediction (especially about compound carcinogenicity). The performance of ADMET predictor results was assessed. The work presented here proposes a computationally driven strategy for designing and discovering a new sulfonamide scaffold for bacterial inhibition.

The anticancer and antibacterial potential of bioactive secondary metabolites derived From bacterial endophytes in association with Artemisia absinthium.

The continuous search for secondary metabolites in microorganisms isolated from untapped reservoirs is an effective prospective approach to drug discovery. In this study, an in-depth analysis was conducted to investigate the diversity of culturable bacterial endophytes present in the medicinal plant A. absinthium, as well as the antibacterial and anticancer potential of their bioactive secondary metabolites. The endophytic bacteria recovered from A. absinthium, were characterized via the implementation of suitable biochemical and molecular analyses. Agar well diffusion and broth microdilution were used to screen antibacterial activity. SEM was performed to assess the impact of the extracted metabolite on MRSA strain cell morphology. Apoptosis and cytotoxicity assays were used to evaluate anticancer activity against MCF7 and A549. The FTIR, GC-MS were used to detect bioactive compounds in the active solvent fraction. Of the various endophytic bacteria studied, P. aeruginosa SD01 showed discernible activity against both bacterial pathogens and malignancies. The crude ethyl acetate extract of P. aeruginosa SD01 showed MICs of 32 and 128 µg/mL for S. aureus and MRSA, respectively. SEM examination demonstrated MRSA bacterial cell lysis, hole development, and intracellular leaking. This study revealed that the crude bioactive secondary metabolite SD01 has potent anticancer activity. In this study, 2-aminoacetophenone, 1,2-apyrazine-1,4-dione, phenazine and 2-phenyl-4-cyanopyridine were the major bioactive secondary metabolites. In conclusion, our findings indicate that the bacteria recovered from A. absinthium plants and in particular, P. aeruginosa SD01 is a remarkable source of untapped therapeutic, i.e., antimicrobial and anticancer compounds.

Homogeneous microwave near-field power focusing using a cylindrical antenna array.

This paper presents an investigation of a microwave near-field power focusing (NFPF) analytical approach utilizing a cylindrical array of electric line sources along the z-axis, applicable to any arbitrary homogeneous linear medium. A novel parameter, termed the "focus ability" (FA), is introduced to quantitatively assess a method's capabilities in achieving power focusing. In the following, the phases and amplitudes of the excitation signals of the array elements are obtained with optimization to maximize FA over a certain studied area. Each stage of the theoretical analysis is supported through COMSOL full-wave simulations, ensuring the validity of the results. Theoretical results relevant to focused power are then compared to outcomes obtained from CST full-wave simulations with the same array configuration while employing half-wave dipole antenna elements with excitations obtained via optimization. These comparisons indicate that the excitation signals obtained by theoretical analysis can be used for power focusing when the array of half-wave dipole antenna sources is utilized. Furthermore, the proposed method leads to a significant reduction in the optimization time. Also, in the provided examples, the FA parameter and NFPF are investigated for the different conditions consisting of the type of the homogeneous medium and the number of antennas.

Effect of smile on facial attractiveness before and after orthodontic treatment in females with more attractive and less attractive facial background.

INTRODUCTION: One of the goals of orthodontic treatment is to improve facial esthetics. This study aimed to determine the effect of smile on facial attractiveness before and after orthodontic treatment in females with "more attractive" and "less attractive" facial backgrounds. In addition, changes in facial attractiveness after orthodontic treatment were examined. METHODS: Frontal rest and smile photographs of 60 female patients (mean age, 26.32 years) before and after orthodontic treatment were included in 4 separate online questionnaires. The link for each questionnaire was sent to 40 layperson raters (20 females, 20 males). They were asked to give a score from 0 to 100 on the basis of the visual analog scale for the attractiveness of each image. Then the data were collected and analyzed. RESULTS: The mean score of the pretreatment smile was significantly smaller than the frontal rest view, and the difference was significantly greater in the "more attractive" group (P = 0.012). After treatment, the smiling view was significantly more attractive than the frontal rest view, and the difference was significantly greater in the "less attractive" group (P = 0.014). In addition, the attractiveness of both smiling and rest views increased significantly after orthodontic treatment, and these changes were significantly greater in the "more attractive" group (P <0.001 and P = 0.011). CONCLUSIONS: An unesthetic pretreatment smile negatively impacted facial attractiveness, and orthodontic treatment significantly improved facial attractiveness. These negative and positive effects were greater in more attractive facial backgrounds.

Almond gum-sodium caseinate complexes for loading propolis extract: Characterization, antibacterial activity, release, and in-vitro cytotoxicity.

Propolis is a natural antioxidant but, its application is limited due to its strong flavor and alcohol-soluble nature. Soluble complexes and coacervates of almond gum (AG) and sodium caseinate (CAS) were produced at pH = 7 and 4.6, respectively for encapsulation of alcoholic extract of propolis. Despite the higher process yield of complexes at pH = 7, the sample at pH = 4.6 indicated higher encapsulation efficiency, antioxidant activity, and total phenolic content. The results of FTIR and XRD supported the interaction of propolis with biopolymeric complexes. Moreover, the thermal stability and antibacterial activity of propolis were improved after encapsulation; propolis showed higher antibacterial activity against Gram-positive than Gram-negative bacteria. Also, encapsulated propolis showed a controlled release in various food simulants and gastrointestinal environments. Apoptosis evaluation and MTT assay confirmed that the encapsulated propolis induces lower cytotoxicity than pure propolis against fibroblast cell line possibly due to the delayed release of propolis.

Targeting and ultrabroad insight into molecular basis of Resistance-nodulation-cell division efflux pumps.

Resistance-nodulation-cell devision (RND) efflux pump variants have attracted a great deal of attention for efflux of many antibiotic classes, which leads to multidrug-resistant bacteria. The present study aimed to discover the interaction between the RND efflux pumps and antibiotics, find the conserved and hot spot residues, and use this information to target the most frequent RND efflux pumps. Protein sequence and 3D conformational alignments, pharmacophore modeling, molecular docking, and molecular dynamics simulation were used in the first level for discovering the function of the residues in interaction with antibiotics. In the second level, pharmacophore-based screening, structural-based screening, multistep docking, GRID MIF, pharmacokinetic modeling, fragment molecular orbital, and MD simulation were utilized alongside the former level information to find the most proper inhibitors. Five conserved residues, containing Ala209, Tyr404, Leu415, Asp416, and Ala417, as well as their counterparts in other OMPs were evaluated as the crucial conserved residues. MD simulation confirmed that a number of these residues had a key role in the performance of the efflux antibiotics; therefore, some of them were hot spot residues. Fourteen ligands were selected, four of which interacted with all the crucial conserved residues. NPC100251 was the fittest OMP inhibitor after pharmacokinetic computations. The second-level MD simulation and FMO supported the efficacy of the NPC100251. It was exhibited that perhaps OMPs worked as the intelligent and programable protein. NPC100251 was the strongest OMPs inhibitor, and may be a potential therapeutic candidate for MDR infections.

Identification of two major direct repeat unit clusters, 8i and 11ce, among methicillin resistant Staphylococcus aureus strains: the emergence of novel dru types and repeats.

BACKGROUND: The changing epidemiology and decreasing susceptibility to first-line antibiotics, such as vancomycin and linezolid, leave clinicians with few therapeutic options for MRSA infections. This study aimed to conduct an epidemiology study and characterize MRSA isolates. METHODS: A total of 150 MRSA isolates were collected from clinical specimens. Antimicrobial susceptibility was determined using the disk diffusion method. Resistance and major virulence genes were screened using the polymerase chain reaction. The SCCmec and dru typing were used to conduct molecular epidemiology. The BioNumerics tandem-repeat sequence typing plug-in tool was utilized for dru type cluster analysis. We constructed a minimum spanning tree using the similarity matrix of the DSI model. RESULTS: We discovered 24 dru types among the 55 dru sequenced MRSA isolates. Additionally, eight new dru types were discovered and added to the dru typing database. Two dru clusters (8i, 11ce) and nine single dru types were identified in 55 dru sequenced MRSA isolates. The two dru clusters, 8i and 11ce, accounted for 46 MRSA isolates (83.63%). The most common one of the nine singles dru types in this study was dt9bd, which belonged to the SCCmec types of IX. CONCLUSIONS: Given that two clusters account for the majority of strains in our study, we can conclude that the genetic origin of these strains is the same. Therefore, the spread of these strains can be prevented with effective MRSA monitoring in hospitals and communities.

Colloidal carriers of almond gum/gelatin coacervates for rosemary essential oil: Characterization and in-vitro cytotoxicity.

The potential of almond gum and gelatin complex coacervates as a colloidal carrier for rosemary essential oil (REO) was investigated along with in-vitro gastrointestinal release and cytotoxicity. The optimum formulation (1 gelatin:2 almond gum and 7% (w/w) REO) was selected based on encapsulation efficiency (43.6%) and encapsulation yield (99.3%). The particle size was 6.9 µm with a high negative zeta-potential (-37.3 mV). FTIR and XRD data revealed that REO was properly loaded within carriers and there were interactions between gelatin and almond gum. Thermal stability of REO was enhanced after complex coacervation according to TGA. REO released slowly from carriers under simulated gastrointestinal fluid. Cytotoxicity of pure REO and REO-loaded complexes was evaluated on 4 T1 cell lines. Encapsulation of REO caused a reduction in toxicity. Overall, coacervates of gelatin-almond gum could be a promising carrier to enhance the application of bioactives in the food and drug industry with low toxicity.

Synthesis of some novel coumarin isoxazol sulfonamide hybrid compounds, 3D-QSAR studies, and antibacterial evaluation.

With the progressive and ever-increasing antibacterial resistance pathway, the need for novel antibiotic design becomes critical. Sulfonamides are one of the more effective antibiotics against bacteria. In this work, several novel sulfonamide hybrids including coumarin and isoxazole group were synthesized in five steps starting from coumarin-3-carboxylic acid and 3-amino-5-methyl isoxazole and assayed for antibacterial activity. The samples were obtained in good to high yield and characterized by FT-IR, 13C-NMR, 1H-NMR, CHN and melting point techniques. 3D-QSAR is a fast, easy, cost-effective, and high throughput screening method to predict the effect of the compound's efficacy, which notably decreases the needed price for experimental drug assay. The 3D-QSAR model displayed acceptable predictive and descriptive capability to find r2 and q2 the pMIC of the designed compound. Key descriptors, which robustly depend on antibacterial activity, perhaps were explained by this method. According to this model, among the synthesized sulfonamide hybrids, 9b and 9f had the highest effect on the gram-negative and gram-positive bacteria based on the pMIC. The 3D-QSAR results were confirmed in the experimental assays, demonstrating that our model is useful for developing new antibacterial agents. The work proposes a computationally-driven strategy for designing and discovering new sulfonamide scaffold for bacterial inhibition.

Expression in eukaryotic cells and purification of synthetic gene encoding enterocin P: a bacteriocin with broad antimicrobial spectrum.

Due to the emergence of multidrug-resistant bacteria, treatment options for infectious diseases are decreasing. Bacteriocins are small antimicrobial peptides produced by numerous bacteria that offer alternative therapeutic strategies to combat multidrug-resistant bacterial infections. We evaluated the cloning, functional expression, and antimicrobial activities of enterocin P (EntP), a class II bacteriocin member, in Chinese hamster ovary (CHO) cells. A synthetic gene matching CHO cell codon usage was designed from the known mature amino acid sequence of EntP and cloned into the protein expression vector pcDNA™3.1(+). CHO cells were transformed with the recombinant plasmid and cultured, and the recombinant protein was purified by affinity chromatography. Antimicrobial activities of the recombinant EntP were evaluated on Gram-positive, Gram-negative, and multidrug-resistant pathogens. Recombinant EntP inhibited growth of a variety of bacteria, including pathogenic species known to cause nosocomial infections, often with multidrug-resistant strains. In addition, recombinant EntP demonstrated broad antimicrobial activities in both high salt medium and human plasma and was stable at high temperatures. The broad antimicrobial activity and stability of EntP make it an attractive therapeutic candidate, particularly for treatment of multidrug-resistant bacterial infections.

Prevalence of Class D Carbapenemases among Extended-Spectrum ß-Lactamases Producing Escherichia coli Isolates from Educational Hospitals in Shahrekord.

INTRODUCTION: Extended-spectrum ß-lactamases (ESBLs) are a set of plasmid-borne, various and quickly evolving enzymes that are a main therapeutic issue now-a-days for inpatient and outpatient treatment. AIM: The aim of this study was to determine multi-drug resistance (MDR) and ESBLs producing E. coli strains, prevalence of class D Carbapenemases among ESBLs producing Escherichia coli isolates from educational hospitals in Shahrekord, Iran. MATERIALS AND METHODS: Uropathogenic Escherichia coli strains were isolated from patients with Urinary Tract Infections (UTIs). The agar disc diffusion test was used to characterize the antimicrobial sensitivity of the E. coli isolates. The ESBL positive strains were identified by phenotypic double-disk synergy test, by third-generation cephalosporin in combination with or without clavulanic acid. Multiplex PCR was carried out for detection of the three families of OXA-type carbapenamases including OXA-23, OXA-24, and OXA-48 in E. coli strains. RESULTS: All bacterial isolates were susceptible to meropenem. Ninety isolates produced ESBL, 55 E. coli isolates from inpatients, and 35 isolates from outpatients, with a significant association (p< 0.05). The prevalence of OXA-23, OXA-24, and OXA-48 in the ESBLs producing isolates was respectively 21%, 18%, and 11% for inpatients, and 10%, 8%, and 6% for outpatients. CONCLUSION: ESBL-producing E. coli isolates are also a major threat in the clinical setting. The findings of this study indicated the high occurrence of ESBLs and multiple antibiotic resistance in E. coli isolates.

Prevalence of Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates in Nosocomial and Community-Acquired Urinary Tract Infections.

BACKGROUND: Klebsiella pneumoniae is a family member of Enterobacteriaceae. Isolates of K. pneumoniae produce enzymes that cause decomposition of third generation cephalosporins. These enzymes are known as extended-spectrum beta-lactamase (ESBL). Resistance of K. pneumoniae to beta-lactamase antibiotics is commonly mediated by beta-lactamase genes. OBJECTIVES: The aim of this study was to identify the ESBL produced by K. pneumoniae isolates that cause community-acquired and nosocomial urinary tract infections within a one-year period (2013 to 2014) in Kashani and Hajar university hospitals of Shahrekord, Iran. PATIENTS AND METHODS: From 2013 to 2014, 150 strains of K. pneumoniae isolate from two different populations with nosocomial and community-acquired infections were collected. The strains were then investigated by double disk synergism and multiplex polymerase chain reaction (PCR). RESULTS: The study population of 150 patients with nosocomial and community-acquired infections were divided to two groups of 75 each. We found that 48 of the K. pneumoniae isolates in the patients with nosocomial infection and 39 isolates in those with community-acquired infections produced ESBL. The prevalence of TEM1, SHV1 and VEB1 in ESBL-producing isolates in nosocomial patients was 24%, 29.3% and 10.6%, and in community-acquired patients, 17.3%, 22.7% and 8%, respectively. CONCLUSIONS: The prevalence of ESBL-producing K. pneumoniae isolate is of great concern; therefore, continuous investigation seems essential to monitor ESBL-producing bacteria in patients with nosocomial and community-acquired infections.