β-lactam antibiotics: An overview from a medicinal chemistry perspective

Abstract β-Lactam antibiotics are one of the most relevant drug classes of antibacterial agents worldwide. The discovery and the market of first β-lactam antibiotic (Penicillin G) is a symbolic landmark of modern chemotherapy. Since then, several other β-lactam antibiotics have been introduced in the therapy, revolutionizing the treatment of bacterial infections. Their antibacterial efficacy has been kept in check by the emergence of bacterial resistance. Among the resistance mechanisms, the expression of β-lactamase enzymes is one of the most studied and prevalent. The combined use of beta-lactamase inhibitors with broad spectrum activity β-lactam antibiotics has been an effective strategy to circumvent the resistance issue. This review discusses, with a focus on structural aspects, the different classes of beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams and penems) in light of their stability, sensitivity to β-lactamases, mechanism of action and spectrum of antimicrobial activity. β-Lactamase inhibitors (structurally correlated and non-correlated to the β-lactam system) and their proposed inhibition mechanisms are also discussed.