Antimicrobial resistance is spreading massively in the world and is becoming one of the main health threats of the 21st century. One of the possible strategies to overcome this problem is to modify the known classes of antibiotics in a rational way, with the aim of tuning their efficacy. In this paper, we present the synthesis and the evaluation of the biological activity of a series of two β-lactam bearing cephalosporin derivatives, in which an additional isolated azetidinone ring, bearing different substituents, is joined to the classical cephalosporanic nucleus by a chain of variable length. A computational approach has been also applied in order to predict the molecular interactions between some representative derivatives and selected penicillin-binding proteins, the natural targets of β-lactam antibiotics. All these derivatives are active against Gram-positive bacteria, with MIC100 comparable or even better than that of the reference antibiotic ceftriaxone, and show no or very low cytotoxic activity on different cell lines. Overall, these molecules appear to be able to exert their activity in particular against microorganisms belonging to some of the species more involved in the development of multidrug resistance.

中文翻译：

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适用于老旧类别的新化合物：两种带有β-内酰胺的头孢菌素的合成及其多学科评价方法。

抗菌素耐药性正在世界范围内广泛传播，并且正在成为21世纪的主要健康威胁之一。解决这个问题的可能策略之一是以合理的方式修改已知类别的抗生素，以期调整其功效。在本文中，我们介绍了一系列两个带有β-内酰胺的头孢菌素衍生物的合成和生物活性的评估，其中另外一个带有不同取代基的分离的氮杂环丁酮环通过一条链连接到经典的头孢菌核。可变长度。为了预测某些代表性衍生物与选定的青霉素结合蛋白（β-内酰胺类抗生素的天然靶标）之间的分子相互作用，还采用了一种计算方法。所有这些衍生物均具有抗革兰氏阳性细菌的活性，MIC100与参考抗生素头孢曲松相比具有甚至更高的MIC100，并且在不同细胞系上均未显示或具有非常低的细胞毒活性。总体而言，这些分子似乎能够发挥其活性，特别是针对属于与多药耐药性发展有关的某些物种的微生物。