Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase.

Bacterial DNA gyrase is an attractive target for the investigation of new antibacterial agents. Inhibitors of the GyrB subunit, which contains the ATP-binding site, are described in this communication. Novel, substituted 5-(1H-pyrazol-3-yl)thiazole compounds were identified as inhibitors of bacterial gyrase. Structure-guided optimization led to greater enzymatic potency and moderate antibacterial potency. Data are presented for the demonstration of selective enzyme inhibition of Escherichia coli GyrB over Staphylococcus aureus GyrB.

Calibration of cameras with radially symmetric distortion.

We present algorithms for plane-based calibration of general radially distorted cameras. By this, we understand cameras that have a distortion center and an optical axis such that the projection rays of pixels lying on a circle centered on the distortion center form a right viewing cone centered on the optical axis. The camera is said to have a single viewpoint (SVP) if all such viewing cones have the same apex (the optical center); otherwise, we speak of NSVP cases. This model encompasses the classical radial distortion model [5], fisheyes, and most central or noncentral catadioptric cameras. Calibration consists in the estimation of the distortion center, the opening angles of all viewing cones, and their optical centers. We present two approaches of computing a full calibration from dense correspondences of a single or multiple planes with known euclidean structure. The first one is based on a geometric constraint linking viewing cones and their intersections with the calibration plane (conic sections). The second approach is a homography-based method. Experiments using simulated and a broad variety of real cameras show great stability. Furthermore, we provide a comparison with Hartley-Kang's algorithm [12], which, however, cannot handle such a broad variety of camera configurations, showing similar performance.

Novel dual-targeting benzimidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent antibacterial activity: intelligent design and evolution through the judicious use of structure-guided design and structure-activity relationships.

The discovery of new antibacterial agents with novel mechanisms of action is necessary to overcome the problem of bacterial resistance that affects all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV are well-characterized clinically validated targets of the fluoroquinolone antibiotics which exert their antibacterial activity through inhibition of the catalytic subunits. Inhibition of these targets through interaction with their ATP sites has been less clinically successful. The discovery and characterization of a new class of low molecular weight, synthetic inhibitors of gyrase and topoisomerase IV that bind to the ATP sites are presented. The benzimidazole ureas are dual targeting inhibitors of both enzymes and possess potent antibacterial activity against a wide spectrum of relevant pathogens responsible for hospital- and community-acquired infections. The discovery and optimization of this novel class of antibacterials by the use of structure-guided design, modeling, and structure-activity relationships are described. Data are presented for enzyme inhibition, antibacterial activity, and in vivo efficacy by oral and intravenous administration in two rodent infection models.