A few atoms make the difference: Synthetic, CD, NMR and computational studies on antiviral and antibacterial activities of glycopeptide antibiotic aglycon derivatives

作者：Bereczki Ilona; Mandi Attila^*; Roth Erzsebet; Borbas Aniko; Fizil Adam; Komaromi Istvan; Sipos Attila; Kurtan Tibor; Batta Gyula; Ostorhazi Eszter; Rozgonyi Ferenc; Vanderlinden Evelien; Naesens Lieve; Sztaricskai Ferenc; Herczegh Pal

来源：European Journal of Medicinal Chemistry, 2015, 94: 73-86.

DOI：10.1016/j.ejmech.2015.02.028

• Teicoplanin aglycon
• Ristocetin aglycon
• Antibacterial
• Antiviral
• Conformation

Despite the close structural similarity between the heptapeptide cores of the glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified derivatives of their aglycons show significantly different antibacterial and antiviral properties. The teicoplanin aglycon derivatives with one exception proved to be potent antibacterials but they did not exhibit anti-influenza virus activity. In contrast, the aglycoristocetin derivatives generally showed high anti-influenza virus activity and possessed moderate antibacterial activity. A systematic structure-activity relationship study has been carried out on ristocetin and teicoplanin aglycon derivatives, to explore which structural differences are responsible for these markedly different biological activities. According to electronic circular dichroism and in silica conformational studies, it was found that the differences in anti-influenza virus activity are mainly determined by the conformation of the heptapeptide core of the antibiotics controlled by the presence or absence of chloro substituents. Knowledge of the bioactive conformation will help to design new analogs with improved anti-influenza virus activity. For the teicoplanin derivatives, it was shown that derivatization to improve the antiviral efficacy was accompanied by a significant decrease in antibacterial activity.

• 出版日期2015-4-13
• 单位河北医科大学