The Odd Couple(s): An Overview of Beta-Lactam Antibiotics Bearing More Than One Pharmacophoric Group

Margherita De Rosa,Anna Verdino,Anna Marabotti,Annunziata Soriente

doi:10.3390/ijms22020617

Margherita De Rosa, Anna Verdino + Show 2 more

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https://doi.org/10.3390/ijms22020617

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Abstract

β-lactam antibiotics are among the most important and widely used antimicrobials worldwide and are comprised of a large family of compounds, obtained by chemical modifications of the common scaffolds. Usually these modifications include the addition of active groups, but less frequently, molecules were synthesized in which either two β-lactam rings were joined to create a single bifunctional compound, or the azetidinone ring was joined to another antibiotic scaffold or another molecule with a different activity, in order to create a molecule bearing two different pharmacophoric functions. In this review, we report some examples of these derivatives, highlighting their biological properties and discussing how this strategy can lead to the development of innovative antibiotics that can represent either novel weapons against the rampant increase of antimicrobial resistance, or molecules with a broader spectrum of action.

Highlights

Abstract: β-lactam antibiotics are among the most important and widely used antimicrobials worldwide and are comprised of a large family of compounds, obtained by chemical modifications of the common scaffolds
Introduction β-lactam antibiotics are a broad group of molecules that are naturally produced by different organisms (Figure 1)
All these compounds share a common chemical moiety, i.e., a four-member ring with an amidic function, commonly called “β-lactam ring” or “azetidinone”. Cephalosporins, and carbapenems, this ring is fused to another 5- or 6-member ring, whereas in monobactams, the β-lactam ring is monocyclic (Figure 1). This moiety is the mainly responsible for the antibacterial properties of all these molecules, due to their ability to block the bacterial cell wall synthesis as a result of their covalent binding to penicillin-binding proteins (PBPs), which are essential enzymes involved in the terminal steps of the synthesis of peptidoglycan, the main component of the bacterial cell wall [9]

Summary

Introduction

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