Indeno[1,2-b]-quinoline carboxylic acids and their dimethylgallium(III) complexes: Evaluation of their efficacy as antibacterial agents

In seeking to meet the ongoing challenge of antimicrobial resistance through novel metallo-based strategies, a series of five indeno[1,2-b]-quinoline carboxylic acids (= RQH; where R is H {not shown}, F, Cl, Br, I and CH₃) and their respective organogallium(III) complexes [GaMe₂(Q)(H₂O)] 1, [GaMe₂(FQ)(H₂O)] 2, [GaMe₂(BrQ)(H₂O)] 3, [GaMe₂(ClQ)(H₂O)] 4, and [GaMe₂(CH₃Q)(H₂O)] 5, have been synthesised, fully characterised, and their antibacterial activity and mammalian cell toxicity studied. Crystallisation from ethanol allowed determination of the solid-state structures of [GaMe₂(Q)(H₂O)] 1 and [{GaMe₂(CH₃Q)}₂(H₂O)(EtOH)]·H₂O 5 A through single crystal X-ray diffraction. The hydrolytic stability of the dimethylgallium(III) complexes was assessed in the biological vehicle solvent DMSO doped with 10 % D₂O. All remained intact in the aqueous environment, indicating a high degree of hydrolytic stability. Complexes 1–5 were evaluated as antibacterial agents towards antibiotic-resistant strains of Klebsiella pneumoniae, KP-1074, KP-AJ289, and KP-RH201207 using a broth microdilution assay. In high iron concentration media (Luria-Bertani broth), conventionally used to grow bacteria, all complexes and the free indenoquinoline carboxylic acids were inactive. When analysed in a low iron medium (RPMI-1640 supplemented with 10 % human serum) however, the complexes were observed to exert antibacterial activity as low as 90 nM (range: 0.09–1.56 μM), whilst the free indenoquinoline carboxylic acids remained inactive.