Antibacterial and antibiofilm activity of 8-Hydroxyquinoline derivatives against Mycobacterium and Staphylococcus species

Abstract

A series of 8-alkoxyquinoline derivatives (QD-1-12) were designed and synthesized on the basis of analogues of 8-hydroxyquinoline (8-HQ) (HQ 1-4). The compounds were evaluated for biofilm inhibition against Mycobacterium smegmatis and Staphylococcus aureus, including antibacterial activity against Mycobacterium tuberculosis, M. smegmatis and S. aureus. Cytotoxicity was evaluated against human monocyte (U937) and African green monkey kidney (Vero) cell lines. The 8-O-prenyl derivative (QD-12) showed a minimum inhibitory concentration (MIC) of 12.5 µM, indicating an approximate 8-fold increased selectivity for the biofilm phenotype and an increased inhibitory activity against methicillin-resistant S. aureus (MRSA) by up to 2-fold. 5,7-Dichloro-8-hydroxy-2-methylquinoline (HQ-2) showed the highest inhibitory potential with MIC values of 0.1, 1.56, 2.2 and 1.1 µM against M. tuberculosis, M. smegmatis, methicillin-sensitive S. aureus (MSSA) and MRSA, respectively. The results indicate the importance of the 8-OH group for antibacterial and antimycobacterial activity. Cytotoxicity revealed low-to-moderate toxicity of 8-HQ (HQ-1). All the compounds, except HQ-1, were tested for the first time for their growth and biofilm inhibitory activity against Mycobacterium spp. and S. aureus.