Discovery of Indeno[1,2-c]quinoline Derivatives as Potent Dual Antituberculosis and Anti-Inflammatory Agents.

A series of indeno[1,2-c]quinoline derivatives were designed, synthesized and evaluated for their anti-tuberculosis (anti-TB) and anti-inflammatory activities. The minimum inhibitory concentration (MIC) of the newly synthesized compound was tested against Mycobacterium tuberculosis H37RV. Among the tested compounds, (E)-N'-[6-(4-hydroxypiperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-ylidene]isonicotino-hydrazide (12), exhibited significant activities against the growth of M. tuberculosis (MIC values of 0.96 µg/mL) with a potency approximately equal to that of isoniazid (INH), an anti-TB drug. Important structure features were analyzed by quantitative structure-activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the anti-TB activity. The anti-inflammatory activity was induced by superoxide anion generation and neutrophil elastase (NE) release using the formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils method. Results indicated that compound 12 demonstrated a potent dual inhibitory effect on NE release and superoxide anion generation with IC50 values of 1.76 and 1.72 µM, respectively. Our results indicated that compound 12 is a potential lead compound for the discovery of dual anti-TB and anti-inflammatory drug candidates. In addition, 6-[3-(hydroxymethyl)piperidin-1-yl]-9-methoxy-11H-indeno[1,2-c]quinolin-11-one (4g) showed a potent dual inhibitory effect on NE release and superoxide anion generation with IC50 values of 0.46 and 0.68 µM, respectively, and is a potential lead compound for the discovery of anti-inflammatory drug candidates.

Automatic measurements of arterial input and venous output functions on cerebral computed tomography perfusion images: a preliminary study.

BACKGROUND: The current automatic techniques for measuring arterial input function (AIF) and venous output (VOF) on cerebral computed tomography perfusion images are prone to motion artifact and random noise, and their failure rates vary between 10% and 65%. We developed a new automatic technique to overcome these problems. METHODS: A principle axis transformation was applied to perfusion images to correct for translational and rotational motion artifacts. Bone voxels and neighboring voxels were removed from the perfusion images. Only brain voxels were included in the AIF and VOF measurement procedures. The selection criteria, such as large area under the concentration-time curve, early arrival of contrast agents, and narrow effective width, were used to select appropriate arterial and venous voxels for the AIF and VOF measurements. The proposed automatic technique was tested in 20 patients with unilateral cerebral arterial stenosis. The results of the proposed technique were compared to the results obtained by manual measurements and commercially available automatic selection software. RESULTS: The AIFs and VOFs were successfully measured using the proposed automatic technique in all 20 patients. The curve shapes, including the area under the concentration-time curve, peak concentration, time to peak, and effective width of the automatically measured AIFs or VOFs were comparable to that were measured manually. CONCLUSION: The proposed automatic measurement technique successfully overcomes the motion artifact and random noise problems encountered in measuring AIF and VOF. It can be easily integrated into software for the automatic calculation of cerebral blood volume and flow.