Oxazolidinone: A promising scaffold for the development of antibacterial drugs

Strategies for the Discovery of Oxazolidinone Antibacterial Agents: Development and Future Perspectives

“…30 These findings suggest the potential of sutezolid as an anti-TB agent, supported by an ongoing phase II study to evaluate its efficacy against tuberculosis. 20,30 Eperezolid (3 in Figure 2B) is a notable example where the morpholine ring of linezolid is replaced with piperazine, with the addition of 2-hydroxyacetamide in the piperazine ring. 31,32 It has emerged as a promising drug candidate for oxazolidinones, displaying stronger antibacterial activity in vitro and superior therapeutic efficacy in vivo compared to linezolid.…”

“…Among the available antibacterial agents, oxazolidinones, including linezolid, represent a novel class of synthetic antibiotics with proven efficacy against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). , Linezolid acts as a bacterial protein synthesis inhibitor by binding to the peptidyl transferase center (PTC) of the 50S ribosomal subunit, distinctively lacking cross-resistance with existing antibiotics. − However, linezolid has certain limitations, such as myelo­suppression, thrombo­cytopenia, lactic acidosis, and neuropathies, when used for an extended period . Additionally, the monoamine oxidase (MAO) inhibitory effects of linezolid can lead to interactions with serotonergic and adrenergic agents, potentially resulting in severe hypertensive crises in patients. , Although the development of linezolid resistance, like linezolid-resistant Staphylococcus aureus (LRSA) and linezolid-resistant Enterococcus faecium (LREFA), is relatively infrequent and stable with prolonged use, this has prompted medicinal chemists to undertake extensive structural modifications of linezolid through various strategies to create novel oxazolidinone antibiotics that exhibit greater activity and improved safety profiles to address these challenges. , For instance, progress in this field has yielded positive outcomes, such as the approval of next-generation oxazolidinone antibiotics like tedizolid phosphate and contezolid, designed for treating diseases associated with Gram-positive bacteria. , …”

Hybridization of antimicrobial oxazolidinones with commercial drugs: A fight against the “superbugs”

“…Oxazolidinone class of antibiotics which contain five membered cyclic carbamate moieties target the bacterial protein synthesis machinery by interacting with 50S ribosomal subunit resulting in the inhibition of the formation of N ‐formyl methionyl‐tRNA, which is precursor to the starting of translation process in bacteria (Yuan et al, 2023). Hybridization of oxazolidinone class of antibiotics with drugs such as furazolidone, pretomanid, fluoroquinolone class of antibiotics, and β‐lactam class of antimicrobials has provided possibilities for targeting the multidrug‐resistant bacteria.…”

Synthesis and Biological Activities of Oxazolidinone Pleuromutilin Derivatives as a Potent Anti-MRSA Agent

“…Modification of the pleuromutilin parent ring is difficult, and the antibacterial activity does not improve significantly. , Some studies have suggested that all pleuromutilin derivatives have a similar binding mode in the tricyclic mutilin core when combined with PTC, while the C-14 side chain varies considerably in the binding position. , In particular, the incorporation of five-membered heterocycles, such as triazole and oxadiazole, into the side chain of pleuromutilin enhances its antibacterial performance. Oxazolidinone is a bioactive fragment that has been introduced as an active functional group in the development of antibacterial drugs with good results. − For example, linezolid, tedizolid, and contezolid have been successively approved, which has greatly increased our interest in introducing these active structures. Furthermore, oxazolidinone has the advantage of containing multiple heteroatoms, which allows it to bind to surrounding receptor residues and improve water solubility.…”

“…Oxazolidinone is a bioactive fragment that has been introduced as an active functional group in the development of antibacterial drugs with good results. 20−22 For example, linezolid, tedizolid, and contezolid have been successively approved, 23 which has greatly increased our interest in introducing these active structures. Furthermore, oxazolidinone has the advantage of containing multiple heteroatoms, which allows it to bind to surrounding receptor residues and improve water solubility.…”