For example, S. aureus has developed mechanisms of resistance against inhibitors that interact with There is substantial research on FabI inhibitors, encompassing diverse chemical scaffolds such as acrylamides, pyridones, diphenyl ethers, tetrahydropyridoindole, pyrolidine, and others (Figure ). The prodrug Afabicin is effective against methicillin-sensitive S. aureus (MSSA) and MRSA and currently is developing a phase II clinical trial in the treatment of staphylococcus infections in bone or joint (NCT03723551) (Debiopharm International SA, 2020). CG400549 (1) completed Phase II clinical trials to assess its safety in multiple doses and pharmacokinetics in patients with cutaneous abscesses caused by MRSA (NCT01593761) . In contrast, the compound MUT056399 (2) has demonstrated antibacterial activity against Gram negative bacteria, including efficacy against methicillinand linezolid-resistant strains . Unlike Afabicin and 1, which are specific to staphylococcal infections, 2 has shown broader efficacy in vivo assays and Phase I clinical trials has been completed to evaluate safety and pharmacokinetics (NCT02295813) ( . Some of the most potent inhibitors of FabI discovered to date are based on indole, diphenyl ether, and pyridone cores. For example, the indole-based inhibitor Figure ) exhibited IC50 of 0.1 μM against S. aureus FabI and IC50 of 4.2 μM against E. coli FabI.