Younis Waleed, AbdelKhalek Ahmed, Mayhoub Abdelrahman S, Seleem Mohamed N
Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN 47906, United States.
Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
Curr Pharm Des. 2017;23(14):2147-2157. doi: 10.2174/1381612823666170209154745.
Bacterial resistance to conventional antibiotics is an increasingly serious threat to public health worldwide that requires immediate exploration and the development of novel antimicrobial compounds. Drug repurposing is an inexpensive and untapped source of new antimicrobial leads, and it holds many attractive features warranting further attention for antimicrobial drug discovery. In an effort to repurpose drugs and explore new leads in the field of antimicrobial drug discovery, we performed a whole-cell screening assay of 1,600 Food and Drug Administration (FDA) approved drugs against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae (ESKAPE) pathogens. The in vitro screening identified 49 non-antimicrobial drugs that were active against at least one species of ESKAPE pathogen. Although some of these drugs were known to have antibacterial activity, many have never been reported before. In particular, sulfonamide-containing structures represent a novel drug scaffold that should be investigated further. The characteristics of these drugs as antimicrobial agents may offer a safe, effective, and quick supplement to current approaches to treating bacterial infections.
细菌对传统抗生素的耐药性对全球公共卫生构成了日益严重的威胁，这需要立即探索和开发新型抗菌化合物。药物重新利用是一种廉价且未被开发的新抗菌先导物来源，它具有许多吸引人的特性，值得在抗菌药物发现领域进一步关注。为了重新利用药物并探索抗菌药物发现领域的新先导物，我们针对粪肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和阴沟肠杆菌（ESKAPE）病原体，对1600种美国食品药品监督管理局（FDA）批准的药物进行了全细胞筛选试验。体外筛选确定了49种对至少一种ESKAPE病原体具有活性的非抗菌药物。虽然其中一些药物已知具有抗菌活性，但许多此前从未被报道过。特别是，含磺胺结构代表了一种应进一步研究的新型药物支架。这些药物作为抗菌剂的特性可能为当前治疗细菌感染的方法提供一种安全、有效且快速的补充。
