In this study, some new compounds, which are 2aminothiadiazole derivatives linked by a phenyl bridge to the 2position of the benzimidazole ring, were designed and synthesized as antimicrobial agents. The structures of the compounds were elucidated by 1 H and 13 C NMR spectroscopy, high-resolution mass spectrometry, and elemental analysis. The antifungal activities of the synthesized compounds were tested on Candida albicans, Candida krusei, Candida glabrata, and Candida parapsilosis. Compound 5f is more active against C. albicans and C. glabrata than standard fluconazole and varicanazole. Compounds were also evaluated for their counteracting activity against Gram-positive Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, and Pseudomonas aeruginosa and Gram-negative Enterococcus faecalis, Bacillus subtilis, and Staphylococcus aureus. Compounds 5c and 5h had minimum inhibitory concentrations against E. faecalis close to that of the standard azithromycin. Molecular docking studies were performed against Candida species' 14-α demethylase enzyme. 5f was the most active compound against Candida species, which gave the highest docking interaction energy. The stabilities of compounds 5c and 5f with CYP51 were tested using 100 ns molecular dynamics simulations. According to the theoretical ADME calculations, the profiles of the compounds are suitable in terms of limiting rules. HOMO−LUMO analysis showed that 5h is chemically more reactive (represented with the lower ΔE = 3.432 eV) than the other molecules, which is compatible with the highest antibacterial activity result.
The accuracy of risk prediction for coronary artery disease can be improved with the use of novel molecular or genetic biomarkers. In this study, we investigated the difference of five selected microRNAs (miR or miRNA) in patients with coronary artery disease (CAD) and controls, assessed by coronary angiography. The study population consisted of 85 subjects, aged between 18 and 75 years and underwent invasive coronary angiography. Subjects with more than 30% stenosis in at least one coronary artery, patients with a history of prior percutaneous coronary intervention or coronary by‐pass surgery were allocated to the patient group; whereas the subjects without at least 30% stenosis consisted the control group. Groups were similar in age, presence of hypertension, and smoking status. However, the proportion of males and subjects taking angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, nitrates, and statins were higher in the patient group. miR‐221 and miR‐155 were downregulated (P = .02 and .001, respectively), while miR‐21 levels were significantly increased (P = .003) in the patient group compared to controls. Changes in miR‐145 and miR‐126 did not reach statistical significance (P > .05). miRNA‐ 21, miR‐155, and miR‐221 were differentially expressed between the patients and controls. miRNAs are promising biomarkers for CAD diagnosis, however, this requires further research with larger groups.
Invasive fungal infections (IFIs) are increasing as major infectious diseases around the world, and the limited efficacy of existing medications has resulted in substantial morbidity and death in patients due to the lack of effective antifungal agents and serious drug resistance. In this study, a series of benzimidazole-1,2,4-triazole derivatives (6a−6l) were synthesized and characterized by 1 H NMR, 13 C NMR, and HR-MS spectral analysis. All the target compounds were screened for their in vitro antifungal activity against four fungal strains, namely, C. albicans, C. glabrata, C. krusei, and C. parapsilopsis. The synthesized compounds exhibited significant antifungal potential, especially against C. glabrata. Three compounds (6b, 6i, and 6j) showed higher antifungal activity with their MIC values (0.97 μg/mL) compared with voriconazole and fluconazole. Molecular docking provided a possible binding mode of compounds 6b, 6i, and 6j in the 14α-demethylase active site. Our studies suggested that the benzimidazole-1,2,4-triazole derivatives can be used as a new fungicidal lead targeting 14α-demethylase for further structural optimization. In addition, their effects on the L929 cell line were also investigated to evaluate the cytotoxic effects of the compounds. SEM analyses were performed to examine the effects of compounds 6a, 6i, and 6j on C. glabrata cells under in vivo experimental conditions.
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