As per the WHO’s “Bacterial Priority Pathogen List”, Carbapenem-resistant A. baumannii (CRAB) is categorized as belonging to the critical priority pathogen group due to the extreme paucity of treatment options (1). A. baumannii causes several nosocomial infections such as pneumonia, sepsis and bacteraemia; skin and soft tissue infections; and meningitis (2). To respond to the urgent and unmet need of identifying novel antibiotics that are active against CRAB, we designed, synthesized and tested 29 naphthalimide derivatives by incorporating the hydrazine group against CRAB BAA-1605. From these compounds, 5b, 5c, 5d and 5e exhibited MICs ranging between 0.5 and 1 μg/ml, and all compounds except 5e displayed >200 selectivity indeces (SIs) against Vero cells. Compound 5d was chosen as a representative and tested against an MDR clinical strain panel, with strains that are resistant to meropenem, levofloxacin and minocycline. In these tests, 5d displayed equi-potent activity. In addition, 5d demonstrated synergy with tobramycin, and the synergy was confirmed by means of a combination time kill assay against CRAB BAA-1605. From the above data, 5d exhibits promise as a potential antibacterial scaffold against CRAB (3).
References:
- https://iris.who.int/bitstream/handle/10665/376776/9789240093461-eng.pdf?sequence=1
- Sieniawski, K., Kaczka, K., Rucinska, M., Gagis, L., & Pomorski, L. (2013). Acinetobacter baumannii nosocomial infections. Polski Przeglad Chirurgiczny/ Polish Journal of Surgery, 85(9), 483–490. https://doi.org/10.2478/pjs-2013-0075
- https://doi.org/10.1039/D4MD00368C
