Development of new anti-bacterial agents acting upon underexploited targets and thus evading known mechanisms of resistance is the need of the hour. The highly conserved and distinct bacterial fatty acid biosynthesis pathway (FAS-II), presents a validated and yet relatively underexploited target for drug discovery. FabI and its isoforms (FabL, FabK, FabV and InhA) are essential enoyl-ACP reductases present in several microorganisms. In addition, the components of the FAS-II pathway are distinct from the multi-enzyme FAS-I complex found in mammals. Thus, inhibition of FabI and its isoforms is anticipated to result in broad-spectrum antibacterial activity. Several research groups from industry and academic laboratories have devoted significant efforts to develop effective FabI-targeting antibiotics, which are currently in various stages of clinical development for the treatment of multi-drug resistant bacterial infections. This review summarizes all the natural as well as synthetic inhibitors of gram-positive and gram-negative enoyl ACP reductases (FabI). The knowledge of the reported inhibitors can aid in the development of broad-spectrum antibacterials specifically targeting FabI enzymes from S. aureus, S. epidermidis, B. anthracis, B. cereus, E. coli, P. aeruginosa, P. falciparum and M. tuberculosis.

迫切需要开发针对未充分利用的目标的新型抗菌剂，从而规避已知的耐药机制。高度保守且独特的细菌脂肪酸生物合成途径（FAS-II）为药物发现提供了经过验证的但相对开发不足的目标。FabI及其同工型（FabL，FabK，FabV和InhA）是存在于几种微生物中的重要烯醇ACP还原酶。另外，FAS-II途径的成分不同于哺乳动物中发现的多酶FAS-I复合物。因此，预期抑制FabI及其同工型会导致广谱抗菌活性。工业界和学术实验室的几个研究小组已致力于开发有效的FabI靶向抗生素，目前正处于临床发展的各个阶段，以治疗多重耐药细菌感染。这篇综述总结了革兰氏阳性和革兰氏阴性烯酰ACP还原酶（FabI）的所有天然和合成抑制剂。所报道的抑制剂的知识可有助于开发专门针对来自的FabI酶的广谱抗菌剂金黄色葡萄球菌，表皮葡萄球菌，炭疽芽孢杆菌，蜡状芽孢杆菌，大肠杆菌，铜绿假单胞菌，恶性疟原虫和结核分枝杆菌。