Synthesis and evaluation of selected benzimidazole derivatives as potential antimicrobial agents

© 2015 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/molecules200815206© 2015 by the authors. A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1Hbenzo[ d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.Published versio

Assessment of knowledge, attitude and practice of diabetic people in Najran, Kingdom of Saudi Arabia

Background: This cross-sectional hospital based study aimed at determining the level of knowledge, attitude and practice of diabetes among local people of Najran, Saudi Arabia.Methods: We aimed to investigate the levels of knowledge, attitude and practice among diabetic people in Najran area.Results: 10% of the participants scored >7, 28% scored >5 and 62% scored 5 and less in Knowledge questionnaire. None [0.00%] of the participants scored 7 or more out of the attitude questionnaire. 100% of the participants scored 5 and less out of 12. 100% of the participants scored >6 and 0% scored 12 or more in the practice questionnaire.Conclusions: Our study revealed that the level of knowledge, attitude and practice of diabetes in the area of Najran is very poor. We suggest that a structured educational program to be adopted by the health authorities in Saudi Arabia

Pharmacoinformatics-based identification of transmembrane protease serine-2 inhibitors from Morus Alba as SARS-CoV-2 cell entry inhibitors

Abstract: Transmembrane protease serine-2 (TMPRSS2) is a cell-surface protein expressed by epithelial cells of specific tissues including those in the aerodigestive tract. It helps the entry of novel coronavirus (n-CoV) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the host cell. Successful inhibition of the TMPRSS2 can be one of the crucial strategies to stop the SARS-CoV-2 infection. In the present study, a set of bioactive molecules from Morus alba Linn. were screened against the TMPRSS2 through two widely used molecular docking engines such as Autodock vina and Glide. Molecules having a higher binding affinity toward the TMPRSS2 compared to Camostat and Ambroxol were considered for in-silico pharmacokinetic analyses. Based on acceptable pharmacokinetic parameters and drug-likeness, finally, five molecules were found to be important for the TMPRSS2 inhibition. A number of bonding interactions in terms of hydrogen bond and hydrophobic interactions were observed between the proposed molecules and ligand-interacting amino acids of the TMPRSS2. The dynamic behavior and stability of best-docked complex between TRMPRSS2 and proposed molecules were assessed through molecular dynamics (MD) simulation. Several parameters from MD simulation have suggested the stability between the protein and ligands. Binding free energy of each molecule calculated through MM-GBSA approach from the MD simulation trajectory suggested strong affection toward the TMPRSS2. Hence, proposed molecules might be crucial chemical components for the TMPRSS2 inhibition. Graphic abstract: [Figure not available: see fulltext.

Antimicrobial Resistance Patterns and ESBL of Uropathogens Isolated from Adult Females in Najran Region of Saudi Arabia

Background: To explore the prevalence of urinary tract infections (UTIs) among female patients in the Najran region of Saudi Arabia and determine their antimicrobial resistance pattern. Methods: This study was conducted on 136 urine samples collected from outpatient departments (OPDs) of the different government hospitals in the Najran region of Saudi Arabia. Over one year, the results of susceptibility testing reports of outpatient midstream urine samples from three government hospitals were prospectively evaluated. Results: Of 136 urine samples, only 123 (90.45%) were found to show significant growth for UTIs, from which 23 different uropathogens were identified. Escherichia coli (58.5%) was the most commonly isolated organism, followed by Klebsiella pneumoniae (8.1%). The isolated microorganism showed increased resistance patterns from 3.3% to 62.6%, with an overall resistance of 27.19%. Meropenem was the most effective antimicrobial, followed by amikacin and ertapenem (0.47%, 0.91%, and 1.5% resistance, respectively). At the same time, ampicillin and cephazolin were the least (62.6% and 59.5% resistance, respectively) effective. Overall, eleven (8.94%) uropathogens isolates were ESBLs, among which there were eight (6.5%) Escherichia coli, one (0.81%) Klebsiella pneumoniae, one (0.81%) Klebsiella oxytoca, and one (0.81%) Citrobacter amalonaticus. Conclusions: E. coli remains the most commonly isolated causative uropathogens, followed by Klebsiella species. The prevalence of pathogenic E. coli and Klebsiella species underscores the importance of developing cost-effective, precise, and rapid identification systems to minimize public exposure to uropathogens. Antibiotic susceptibility data revealed that most of the isolates were resistant to the majority of the antibiotics. The patients with UTIs in the Najran region of Saudi Arabia are at a high risk of antibiotic resistance, leading to significant problems in outpatient department (OPD) treatment outcomes and raising the alarm for the physician to change their empiric treatment

أصول المصادر في المعرفة: دراسة منهجية

The knowledge theory is an important discussion and the most important theme of these theories is about the source of knowledge, which received a broad debate in modern Western thought. It has become excessive because of its drawback behind the secular visions, in some sources, such as reason and sense, as well as marginalization of flaws in thought at all times and places. One of the ways to deal with this issue: promoting moderatism in ideas and thoughts that lead to justice and excellence. The research methodology is based on a combination of analytical, structural, and critical approaches. The results highlight the importance of finding sources of knowledge, there is no knowledge without sources, the importance of determining the scope work of each source, examining the sources through five aspects, which are information, logic, sense, persons, and intuition. By looking at the sources integrally, and that religion should become the source of knowledge because it comes from a divine revelation. Sources of knowledge that come from human will not be useful unless they are related to the light of revelation

Enhancing the performance of lightweight configurable PUF for robust IoT hardware-assisted security

Lightweight physical unclonable functions (LPUFs) exploit manufacturing process variations of semiconductor integrated circuits (ICs) to protect IoT-based electronic and smart devices from new cyberattacks. This paper proposes two novel security techniques to enhance the robustness of LPUFs using configurable-based ring oscillator PUFs (CF-ROPUFs). These techniques are the intra-die frequency aware (IFA) approach to improve PUF reliability and the logarithmic gamma function ( Ln_\gamma ) technique to enhance PUF randomness. The lightweight CF-ROPUF design is realized on hardware, and data samples are collected under varying temperatures and supply voltages over a population of 30 Spartan-3E FPGAs. Experimental results of the IFA technique in terms of average Hamming Weight (HM) demonstrate that the percentage of the reliable RO sample frequencies PUF output is 98.5%. For the analysis, PUF reliability is evaluated in terms of accuracy, repeatability, and reproducibility, the international organization for Standardization (ISO) standards. The results indicate that the RO samples are accurately measured from the CF-ROPUFs mapped in all the chips. After using the proposed 1-out-of-r coding algorithm, the results demonstrate high average repeatability of 98.2% and a magnified average reproducibility of 99.63%. It is also shown that our CF-ROPUF design is immune from accelerated aging impacts reliability issues. Statistical results show that Ln( Ln_γ) enhances the normality and mitigate the negative impacts of the systematic process variations on RO sample frequencies. Randomness results show that CF-ROPUF binary response bits can successfully pass the 15 NIST test suites for true randomness with an enhanced percentage, 93.3%, with the application of the 1-out-of-r coding

Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent

Pharmacoinformatics-based identification of transmembrane protease serine-2 inhibitors from Morus Alba as SARS-CoV-2 cell entry inhibitors

Transmembrane protease serine-2 (TMPRSS2) is a cell-surface protein expressed by epithelial cells of specific tissues including those in the aerodigestive tract. It helps the entry of novel coronavirus (n-CoV) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the host cell. Successful inhibition of the TMPRSS2 can be one of the crucial strategies to stop the SARS-CoV-2 infection. In the present study, a set of bioactive molecules from Morus alba Linn. were screened against the TMPRSS2 through two widely used molecular docking engines such as Autodock vina and Glide. Molecules having a higher binding affinity toward the TMPRSS2 compared to Camostat and Ambroxol were considered for in-silico pharmacokinetic analyses. Based on acceptable pharmacokinetic parameters and drug-likeness, finally, five molecules were found to be important for the TMPRSS2 inhibition. A number of bonding interactions in terms of hydrogen bond and hydrophobic interactions were observed between the proposed molecules and ligand-interacting amino acids of the TMPRSS2. The dynamic behavior and stability of best-docked complex between TRMPRSS2 and proposed molecules were assessed through molecular dynamics (MD) simulation. Several parameters from MD simulation have suggested the stability between the protein and ligands. Binding free energy of each molecule calculated through MM-GBSA approach from the MD simulation trajectory suggested strong affection toward the TMPRSS2. Hence, proposed molecules might be crucial chemical components for the TMPRSS2 inhibition.https://link.springer.com/journal/11030hj2022Chemical Patholog