Stereochemical modification of geminal dialkyl substituents on pantothenamides alters antimicrobial activity.

Pantothenamides are N-substituted pantothenate derivatives which are known to exert antimicrobial activity through interference with coenzyme A (CoA) biosynthesis or downstream CoA-utilizing proteins. A previous report has shown that replacement of the ProR methyl group of the benchmark N-pentylpantothenamide with an allyl group (R-anti configuration) yielded one of the most potent antibacterial pantothenamides reported so far (MIC of 3.2 µM for both sensitive and resistant Staphylococcus aureus). We describe herein a synthetic route for accessing the corresponding R-syn diastereomer using a key diastereoselective reduction with Baker's yeast, and report on the scope of this reaction for modified systems. Interestingly, whilst the R-anti diastereomer is the only one to show antibacterial activity, the R-syn isomer proved to be significantly more potent against the malaria parasite (IC50 of 2.4±0.2 µM). Our research underlines the striking influence that stereochemistry has on the biological activity of pantothenamides, and may find utility in the study of various CoA-utilizing systems.

Attenuation of Hemodynamic Responses to Laryngoscopy and Tracheal Intubation: Propacetamol versus Lidocaine-A Randomized Clinical Trial.

The purpose of this study is to assess the effects of propacetamol on attenuating hemodynamic responses subsequent laryngoscopy and tracheal intubation compared to lidocaine. In this randomized clinical trial, 62 patients with the American Anesthesiologists Society (ASA) class I/II who required laryngoscopy and tracheal intubation for elective surgery were assigned to receive propacetamol 2 g/I.V./infusion (group P) or lidocaine 1.5 mg/kg (group L) prior to laryngoscopy. Systolic and diastolic blood pressures (SBP, DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded at baseline, before laryngoscopy and within nine minutes after intubation. In both groups P and L, MAP increased after laryngoscopy and the changes were statistically significant (P < 0.001). There were significant changes of HR in both groups after intubation (P < 0.02), but the trend of changes was different between two groups (P < 0.001). In group L, HR increased after intubation and its change was statistically significant within 9 minutes after intubation (P < 0.001), while in group P, HR remained stable after intubation (P = 0.8). Propacetamol 2 gr one hour prior intubation attenuates heart rate responses after laryngoscopy but is not effective to prevent acute alterations in blood pressure after intubation.