A new DNA gyrase inhibitor subclass of the cyclothialidine family based on a bicyclic dilactam-lactone scaffold. Synthesis and antibacterial properties.

The DNA gyrase inhibitor cyclothialidine had been shown to be a valuable lead structure for the discovery of new antibacterial classes able to overcome bacterial resistance to clinically used drugs. Bicyclic lactone derivatives containing in their 12-14-membered ring a thioamide functionality were reported previously to exhibit potent antibacterial activity against gram-positive bacteria. Moderate in vivo efficacy, however, was demonstrated only for derivatives bearing hydrophilic substituents, which were found to have a favorable impact on pharmcokinetics, and to reduce metabolic degradation, in particular glucuronidation.

New antibacterial agents derived from the DNA gyrase inhibitor cyclothialidine.

Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products. It acts by competitively inhibiting the ATPase activity exerted by the B subunit of DNA gyrase but barely exhibits any growth inhibitory activity against intact bacterial cells, presumably due to insufficient permeation of the cytoplasmic membrane. To explore the antibacterial potential of 1, we developed a flexible synthetic route allowing for the systematic modification of its structure.

Venous pressure in idiopathic varicocele.

In 27 patients with clinically identified idiopathic left varicocele, a retrograde venography and a combined pressure measurement in the vena cava, vena renalis and vena spermatica was performed. During Valsalva maneuver the pressure values increased. We could not confirm increased pressure values in the left renal vein dependent on the patient's position.

[Gluing of the Achilles tendon with a fibrin adhesive].

Reported in this paper are clinical findings and results obtained from follow-up checks, using computed tomography, in the wake of fibrin adhesive treatment of Achilles tendon ruptures. Complaints had almost completely disappeared from 27 in 35 patients who had undergone the above operations, between 1981 and 1985. These findings were confirmed by functional follow-up examinations.