According to the World Health Organization (WHO), approximately 1.7 million deaths per year are caused by tuberculosis infections. Furthermore, it has been predicted that, by 2050, antibacterial resistance will be the cause of approximately 10 million deaths annually if the issue is not tackled. As a result, novel approaches to treating broad-spectrum bacterial infections are of vital importance. During the course of our wider efforts to discover unique methods of targeting multidrug-resistant (MDR) pathogens, we identified a novel series of amide-linked pyrimido[4,5-b]indol-8-amine inhibitors of bacterial type II topoisomerases. Compounds from the series were highly potent against gram-positive bacteria and mycobacteria, with excellent potency being retained against a panel of relevant Mycobacterium tuberculosis drug-resistant clinical isolates.

根据世界卫生组织（WHO）的数据，每年约有170万人死于肺结核感染。此外，据预测，到2050年，如果不解决该问题，则抗菌药耐药性将每年导致约1000万人死亡。结果，治疗广谱细菌感染的新方法至关重要。在我们为发现针对多药耐药性（MDR）病原体的独特方法的更广泛努力的过程中，我们鉴定了细菌II型拓扑异构酶的酰胺连接的嘧啶并[4,5 - b ]吲哚-8-胺抑制剂系列。该系列化合物对革兰氏阳性细菌和分枝杆菌具有很高的效力，而对一系列相关的化合物则保持了出色的效力结核分枝杆菌耐药的临床分离株。