Structure-activity relationship studies on the inhibition of the bacterial translation of novel Odilorhabdins analogues.

A structure-activity relationship (SAR) study of NOSO-95179, a nonapeptide from the Odilorhabdin class of antibacterials, was performed by systematic variations of amino acids in positions 2 and 5 of the peptide. A series of non-proteinogenic amino acids was synthesized in high enantiomeric purity from Williams' chiral diphenyloxazinone by highly diastereoselective alkylation or by aldol-type reaction. NOSO-95179 analogues for SAR studies were prepared using solid-phase peptide synthesis. Inhibition of bacterial translation by each of the synthesized Odilorhabdin analogues was measured using an in vitro test. For the most efficient analogues, antibacterial efficacy was measured against two wild-type Enterobacteriaceae (Escherichia coli and Klebsiella pneumoniae) and against an efflux defective E. coli strain (ΔtolC) to evaluate the impact of efflux on the antibacterial activity.

Double-sleeve and carinal resections using the uniportal VATS technique: a single centre experience.

BACKGROUND: Video-assisted thoracic surgery (VATS) double-sleeve lobectomy and carinal resections are two of the most complex procedures in thoracic surgery. The uniportal approach provides an advantage for performing these procedures successfully; however, knowledge of the important technical details is required. This study describes the experience of implementing these procedures by Russian specialists. METHODS: Six patients (one woman; mean age, 57.3±3.6 years) who underwent a uniportal VATS double sleeve and carinal resections were consecutively included in this study. A 5- to 6-cm incision was made at the fifth intercostal space on the middle axillary line. RESULTS: Double sleeve left upper lobectomy was completed in four cases. One case of the right sleeve carinal pneumonectomy and one case of the right sleeve carinal upper lobectomy were completed. The mean operation time was 280±13 minutes. There was no conversion to thoracotomy. The mean postoperative hospital stay was 10.8±0.8 days. There was no postoperative mortality. In one case of double-sleeve lobectomy, postoperative pneumonia developed. The postoperative diagnoses of the four uniportal double-sleeve cases were as follows: T2aN2M0 in one case, T3N1M0 in two cases, and T2aN0M0 in one case. The postoperative diagnoses of the two uniportal totally carinal resections were as follows: T4N0M0 and T3N0M0. CONCLUSIONS: This study results suggest that a uniportal VATS approach might be a feasible option for complex sleeve resections with acceptable postoperative outcomes in the advanced stages of lung cancer. To further evaluate the feasibility, safety, and efficacy of this technique, more experience would be required.

Robotic sequential analysis of a library of metalloporphyrins as electrocatalysts for voltammetric nitric oxide sensors.

A library of 83 metalloporphyrins with varying substitution pattern at the meso-position of the porphyrins and different central metal ions in the core region has been synthesized in small quantities using a parallel synthesis strategy. By means of a specially designed electrochemical robotic device integrating a 96-well microtitre plate and an easily movable assembly of working, counter and reference electrodes, the different porphyrins were automatically applied in sequence to an in-well electrochemical preparation and testing of NO sensors. Screening the entire compound collection suggested initial considerations concerning the influence of varied functionalities of the metalloporphyrins on their electrocatalytic properties for the oxidation of NO and helped to identify the quality of the investigated catalyst candidates. As compared to manually performed quality tests, the proposed strategy of automation has advantages in convenience, rapidity and especially reproducibility avoiding any inaccuracies introduced by manually performing all steps of the complex sensor formation and testing sequence.

Palladium-catalyzed arylation and heteroarylation of indolizines.

A highly effective protocol for palladium-catalyzed selective arylation and heteroarylation of indolizines at C-3 has been developed. Mechanistic studies unambiguously support an electrophilic substitution pathway for this transformation.