Verdino Anna, Vigliotta Giovanni, Giordano Deborah, Caputo Ivana, Soriente Annunziata, De Rosa Margherita, Marabotti Anna
Department of Chemistry and Biology "A. Zambelli", University of Salerno, Fisciano (SA), Italy.
PLoS One. 2017 Jul 27;12(7):e0181563. doi: 10.1371/journal.pone.0181563. eCollection 2017.
We present the synthesis and biological evaluation of the prototype of a new class of cephalosporins, containing an additional isolated beta lactam ring with two phenyl substituents. This new compound is effective against Gram positive microorganisms, with a potency similar to that of ceftriaxone, a cephalosporin widely used in clinics and taken as a reference, and with no cytotoxicity against two different human cell lines, even at a concentration much higher than the minimal inhibitory concentration tested. Additionally, a deep computational analysis has been conducted with the aim of understanding the contribution of its moieties to the binding energy towards several penicillin-binding proteins from both Gram positive and Gram negative bacteria. All these results will help us developing derivatives of this compound with improved chemical and biological properties, such as a broader spectrum of action and/or an increased affinity towards their molecular targets.
我们展示了一类新型头孢菌素原型的合成及生物学评价，该原型含有一个带有两个苯基取代基的额外孤立β-内酰胺环。这种新化合物对革兰氏阳性微生物有效，其效力与头孢曲松相似，头孢曲松是临床上广泛使用的一种头孢菌素并用作参考，并且即使在远高于测试的最小抑菌浓度的浓度下，对两种不同的人类细胞系也没有细胞毒性。此外，还进行了深入的计算分析，目的是了解其各部分对与革兰氏阳性和革兰氏阴性细菌的几种青霉素结合蛋白的结合能的贡献。所有这些结果将有助于我们开发具有改进的化学和生物学特性的该化合物衍生物，例如更广泛的作用谱和/或对其分子靶点的亲和力增加。
