Previous research has shown that the use of negative emotions such as sadness in donation appeals can make people empathetic towards the donation target, increasing their tendency to donate (the “empathy‐helping” hypothesis). In this research we propose an “inspiration‐helping” hypothesis, and find that the positive emotion of strength can inspire people to donate. We show that combining the positive emotion of strength and the negative emotion of sadness is more effective as a means of persuading people to donate than the sadness‐dominating or the strength‐dominating emotion.
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.
Pleuromutilins were discovered as natural-product antibiotics in 1950. The modifications of pleuromutilin lead to the successful development of veterinary medicines such as tiamulin and valnemulin. Retapamulin became the first pleuromutilin approved for use in human skin infections. Recent advances have led to the synthesis of pleuromutilins that combine potent antibacterial activity with favorable pharmaceutical properties, and three new pleuromutilins, BC-3781, BC-3205 and BC-7013, have entered clinical trials. In this review, the key pleuromutilin derivatives, as well as related novel derivatives during 2009-2013, and its antibacterial activities, are presented. Moreover, the antibacterial and resistance mechanism are discussed.
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