A series of novel pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae were tested by the agar dilution method and Oxford cup assay. The majority of the tested compounds displayed moderate antibacterial activities. Importantly, the three compounds with amino or tertiary amine groups in their side chains, 11, 13b, and 15c, were the most active antibacterial agents. Docking experiments carried out on the peptidyl transferase center (PTC) of 23S rRNA proved that there is a reasonable direct correlation between the binding free energy (ΔGb, kcal/mol) and the antibacterial activity. Moreover, the pharmacokinetic profiles of 11 and 15c in rat were characterized by moderate clearance and oral bioavailability.

BackgroundACDF is the standard procedure for treatment of cervical spondylotic myelopathy (CSM), but a long-term follow-up has been revealed some associated complications of swallowing discomfort, displacement of the fusion device, and accelerated degeneration of the adjacent segment.ObjectiveTo evaluate the clinical outcomes of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) for single-segment CSM and to analyze the clinical efficacy, surgical characteristics, and complication prevention.MethodsA total of 32 patients who underwent APFETDSC for single-segment CSM from Aug. 2015 to Apr. 2017 were reviewed. Operating time, time of walking out of bed postoperation, length of hospitalization, complications, neck pain visual analog scale (VAS), and Japanese Orthopaedic Association Score (JOA) were evaluated. Measurement of intervertebral height (HI) of surgical segments on cervical neutral X-ray, Harrison’s method was used to measure cervical spine angle (CSA).ResultsThe operation time was 103.3 ± 12.95 min, time of walking out of bed after surgery was 19.81 ± 4.603 h, the length of postoperative hospital stay was 57.48 ± 19.48 h. The postoperative neck pain VAS and JOA were significantly improved compared with preoperation(p < 0.001). The postoperative HI was statistical significance decreased compared with preoperation(p < 0.001), but the HI reduction was less than 0.5 mm, without adverse clinical symptoms. The postoperative CSA was significantly improved compared with preoperative(p < 0.001). The excellent and good rate was 87.5%, and the JOA improvement rate was 75.52 ± 11.11%. There was no cervical instability, vertebral fracture, wound infection, and other complications.ConclusionsAPFETDSC is a safe and effective minimally invasive technique with small auxiliary injuries for single-segment CSM while avoiding the sequelae of ACDF. Its short-term clinical efficacy was good and no significant effect on cervical stability.

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A strategy concerning the synthesis of 2-substituted benzo[b]furan compounds from o-alkynyl phenols via a gold-catalyzed alkyne hydroxylation is described, which allows the rapid synthesis of various 2-substituted benzo [b]furan derivatives in excellent yields under mild conditions. The o-alkynyl phenol precursors were readily prepared with a Sonogashira coupling reaction.