Monobactams: A unique natural scaffold of four-membered ring skeleton, recent development to clinically overcome infections by multidrugresistant microbes

Background: Monobactam antibiotics have been testified to demonstrate significant antibacterial activity especially the treatment of infections by superbug microbes. Recently, research has been focused on the structural modifications, and new generation of this privileged natural scaffold. Objective: Efforts have been made to discover the structure-antibacterial relationship of monbactams in order to avoid the aimless work involving the ongoing generated analogues. This review aims to summarize the current knowledge and development of monobactams as a broad-spectrum antibacterial scaffolds. The recent structural modifications that expand the activity, especially in the infections by resistant-strains, combinational therapies and dosing, as well as the possibility of crosshypersensitivity/ reactivity/tolerability with penicillins and cephalosporins will also be summarized and inferred. Different approaches will be covered with emphasis on chemical methods and Structure- Activity Relationship (SAR), in addition to the proposed mechanisms of action. Clinical investigation of monobactams tackling various aspects will not be missed in this review. Conclusion: The conclusion includes the novels approaches, that could be followed to design new research projects and reduce the pitfalls in the future development of monobactams.