Rapid Assembly of Pyrrole-Ligated 1,3,4-Oxadiazoles and Excellent Antibacterial Activity of Iodophenol Substituents.

Pyrrole-ligated 1,3,4-oxadiazole is a very important pharmacophore which exhibits broad therapeutic effects such as anti-tuberculosis, anti-epileptic, anti-HIV, anti-cancer, anti-inflammatory, antioxidant, and antibacterial activities. A one-pot Maillard reaction between D-Ribose and an L-amino methyl ester in DMSO with oxalic acid at 2.5 atm and 80 °C expeditiously produced pyrrole-2-carbaldehyde platform chemicals in reasonable yields, which were utilized for the synthesis of pyrrole-ligated 1,3,4-oxadiazoles. Benzohydrazide reacted with the formyl group of the pyrrole platforms to provide the corresponding imine intermediates, which underwent I2-mediated oxidative cyclization to the pyrrole-ligated 1,3,4-oxadiazole skeleton. The structure and activity relationship (SAR) of the target compounds with varying alkyl or aryl substituents of the amino acids and electron-withdrawing or electron-donating substituents on the phenyl ring of benzohydrazide were evaluated for antibacterial activity against Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii as representative Gram(-) and Gram(+) bacteria. Branched alkyl groups from the amino acid showed better antibacterial activities. Absolutely superior activities were observed for 5f-1 with an iodophenol substituent against A. baumannii (MIC < 2 µg/mL), a bacterial pathogen that displays a high resistance to commonly used antibiotics.

Usefulness of Three-Dimensional Iodine Mapping Quantified by Dual-Energy CT for Differentiating Thymic Epithelial Tumors.

Background: Dual-energy CT has been reported to be useful for differentiating thymic epithelial tumors. The purpose is to evaluate thymic epithelial tumors by using three-dimensional (3D) iodine density histogram texture analysis on dual-energy CT and to investigate the association of extracellular volume fraction (ECV) with the fibrosis of thymic carcinoma. Methods: 42 patients with low-risk thymoma (n = 20), high-risk thymoma (n = 16), and thymic carcinoma (n = 6) were scanned by dual-energy CT. 3D iodine density histogram texture analysis was performed for each nodule on iodine density mapping: Seven texture features (max, min, median, average, standard deviation [SD], skewness, and kurtosis) were obtained. The iodine effect (average on DECT180s-average on unenhanced DECT) and ECV on DECT180s were measured. Tissue fibrosis was subjectively rated by one pathologist on a three-point grade. These quantitative data obtained by examining associations with thymic carcinoma and high-risk thymoma were analyzed with univariate and multivariate logistic regression models (LRMs). The area under the curve (AUC) was calculated by the receiver operating characteristic curves. p values < 0.05 were significant. Results: The multivariate LRM showed that ECV > 21.47% in DECT180s could predict thymic carcinoma (odds ratio [OR], 11.4; 95% confidence interval [CI], 1.18-109; p = 0.035). Diagnostic performance was as follows: Sensitivity, 83.3%; specificity, 69.4%; AUC, 0.76. In high-risk thymoma vs. low-risk thymoma, the multivariate LRM showed that the iodine effect ≤1.31 mg/cc could predict high-risk thymoma (OR, 7; 95% CI, 1.02-39.1; p = 0.027). Diagnostic performance was as follows: Sensitivity, 87.5%; specificity, 50%; AUC, 0.69. Tissue fibrosis significantly correlated with thymic carcinoma (p = 0.026). Conclusions: ECV on DECT180s related to fibrosis may predict thymic carcinoma from thymic epithelial tumors, and the iodine effect on DECT180s may predict high-risk thymoma from thymoma.