Novel Benzimidazole-Based Compounds as Antimicrobials: Synthesis, Molecular Docking, Molecular Dynamics and in silico ADME Profile Studies.

Some novel benzimidazole derivatives were synthesized and their antimicrobial activities were evaluated. Compounds 3a and 3b exhibited excellent antibacterial activity with MIC values <4 µg/mL against Staphylococcus aureus ATCC 29213 (MSSA) and Staphylococcus aureus ATCC 43300 (MRSA). Molecular docking analyzes of compounds with MIC values of 16 µg/mL and below against gram-positive bacteria and fungi were performed using FabH (ß-ketoacyl-acyl carrier protein synthase III) as bacterial protein and CYP51 (sterol 14α-demethylase) as the fungal target protein. According to the molecular docking analysis, it was calculated that sufficient protein-ligand interaction energy was liberated between the compounds 2f, 3a, 3b, 3e and 3h and the antibacterial target protein FabH and strong interactions were formed between 2f and 3h and the antifungal target protein. According to RMSD, RMSF and MMPBSA measurements obtained from molecular dynamics, it is understood that compounds 3a and 3b maintain protein-ligand stability in silico physiological conditions.

The effects of antidepressants fluoxetine, sertraline, and amitriptyline on the development of antibiotic resistance in Acinetobacter baumannii.

This study investigates the effects of antidepressants fluoxetine, sertraline, and amitriptyline on the development of antibiotic resistance in clinical Acinetobacter baumannii isolates. The isolates were exposed to fluoxetine, sertraline, and amitriptyline for 30 days, respectively. The bacteria that developed resistance to gentamicin, imipenem, colistin, and ciprofloxacin were isolated and expression levels of some antibiotic-resistance genes were determined by quantitative reverse-transcriptase PCR. Before and after the exposure, minimum inhibitory concentration (MIC) values of the bacteria were determined by the microdilution method. The statistical analysis was performed using Student's t test. A time-dependent increase was observed in the number of bacteria that developed resistance and increased the MIC value. After exposure to fluoxetine and sertraline, decreases were observed for efflux and outer membrane porin genes in isolates that developed colistin resistance, and increases were observed in isolates that developed ciprofloxacin resistance. These observations suggest that these antidepressants have similar effects on the development of resistance. While the exposure to fluoxetine did not result in the development of resistance to imipenem, it was observed after exposure to sertraline and amitriptyline, and a common decrease in ompA gene expression was determined in these isolates. To our knowledge, the comparative effects of selected antidepressants on the development of antibiotic resistance in A. baumannii are reported and presented in the literature here for the first time.

Antimicrobial Activities of Some Pyrazoline and Hydrazone Derivatives.

OBJECTIVES: Resistance to antibiotics is recognized as one of the biggest threats to human health worldwide. Frequent and unnecessary use of antibiotics has caused infectious agents to adapt to antibiotics and thus drugs have become less effective. The resistance to many antibiotics necessitates the discovery of new antibiotics. In this study, two new and 23 previously reported 2-pyrazoline derivatives and one hydrazone derivative were evaluated for their in vitro antibacterial and antifungal activities. MATERIALS AND METHODS: For the determination of the minimum inhibitory concentration (MIC) values of compounds, microbroth dilution was used. RESULTS: The antimicrobial activities of the compounds were found in a wide range with MIC values of 32-512 µg/mL. CONCLUSION: The synthesized compounds showed moderate antimicrobial activity compared with the standards. They can be used as lead molecules for the synthesis of more effective compounds.

Molecular Identification and Antimicrobial Activity of Vaginal Lactobacillus sp.

BACKGROUND: The genus Lactobacillus has recently been the focal point of researchers due to their ability to produce secondary metabolites with antimicrobial effects. OBJECTIVE: The aim of this study was to identify vaginal Lactobacillus sp. by analyzing 16S rRNA gene sequence, to investigate into antimicrobial activities of secondary metabolites produced by these isolates and to determine the quantities of lactic acid, acetic acid and hydrogen peroxide in secondary metabolites using High-Performance Liquid Chromatography. METHODS: Antimicrobial activities of secondary metabolites were investigated against test microorganisms using Agar Well Diffusion and Agar Spot Methods. RESULTS: According to the results, 18 L. crispatus, 17 L. gasseri, 5 L. jensenii, 4 L. vaginalis, 3 L. fermentum, 2 L. coleohominis, 1 L. saerimneri, 1 L. reuteri, 1 L. johnsonii and 1 L. helveticus were identified. Isolates were frequently found to be effective against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae RSKK 578 and Bacillus subtilis ATCC 6633. None of the isolates showed activity against Staphylococcus aureus ATCC 43300, S. epidermidis ATCC 12228, S. epidermidis ATCC 35984 and Candida albicans ATCC 10231. Secondary metabolites of all tested isolates contain hydrogen peroxide between 7.306 and 0.33 µg/µL range. CONCLUSION: It was found that the secondary metabolites of some isolates contained both acetic and lactic acid, while some of them contained either acetic or lactic acid.