The flavone backbone is a well-known pharmacophore present in a number of substrates and inhibitors of various P450 enzymes. In order to find highly potent and novel P450 family I enzyme inhibitors, an acetylene group was incorporated into six different positions of flavone. The introduction of an acetylene group at certain locations of the flavone backbone lead to time-dependent inhibitors of P450 1A1. 3′-Ethynylflavone, 4′-ethynylflavone, 6-ethynylflavone, and 7-ethynylflavone (KI values of 0.035–0.056 μM) show strong time-dependent inhibition of P450 1A1, while 5-ethynylflavone (KI value of 0.51 μM) is a moderate time-dependent inhibitor of this enzyme. Meanwhile, 4′-ethynylflavone and 6-ethynylflavone are highly selective inhibitors toward this enzyme. Especially, 6-ethynylflavone possesses a Ki value of 0.035 μM for P450 1A1 177- and 15-fold lower than those for P450s 1A2 and 1B1, respectively. The docking postures observed in the computational simulations show that the orientation of the acetylene group determines its capability to react with P450s 1A1 and 1A2. Meanwhile, conformational analysis indicates that the shape of an inhibitor determines its inhibitory selectivity toward these enzymes.
Purpose To evaluate the reduction of out-of-field artifacts caused by body parts outside the field of view (FOV) at rapid kVp switching dual energy CT (rsDECT). Materials and methods This retrospective study was approved by our institutional review board. Informed consent was not required. We viewed 246 consecutive rsDECT thoracoabdominal scans to identify those with body parts outside the maximal FOV of 50 cm. The maximal length, thickness and subjective severity of the out-of-field artifacts were recorded for the 40, 65 and 140 keV virtual monochromatic and the iodine and water density images. Artifact severity was rated on a 5 point scale from 0=absent to 5=obscures intraabdominal/intrathoracic anatomic detail. Artifact thickness and severity scores were compared by t-test and Wilcoxon tests, respectively. Results In 20 of 246 scans (8.1%), body parts extended past the maximum FOV of 50 cm. The mean BMI of these 20 patients was 40.2 kg/m2 (range, 26.83 to 61.69 kg/m2), and out-of-field artifacts occurred for all 20. The mean out-of-field artifact maximal length was 16.6 cm. The mean artifact thickness was significantly less for iodine density (0.6 mm) than for the 65 keV and water density images (8.4 and 13.5 mm, respectively, p<0.001 each comparison). The mean artifact severity score was lower for iodine density (0.2) than for the 65 keV and water density images (2.5 and 2.6, respectively, p<0.001 each). Conclusion Iodine density images reduce out-of-field image artifact at rsDECT and assists in the evaluation of peripheral tissues that extend beyond the maximal CT FOV.
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