N-Alkyl-2-Quinolonopyrones Demonstrate Antimicrobial Activity against ESKAPE Pathogens Including Staphylococcus aureus

Abstract

Antibiotic resistance has grown significantly in the last three decades, while research and development of new antibiotic classes has languished. Therefore, new chemical frameworks for the control of microbial behavior are urgently required. This study presents a novel suite of compounds, based on a tricyclic 4-hydroxy-2 H -pyrano[3,2- c ]quinoline-2,5(6 H )-dione core, with significant antibiotic activity against the ESKAPE pathogens Staphylococcus aureus and Enterococcus faecalis and the “accidental pathogen” Staphylococcus epidermidis . A potent analogue with an N -heptyl-9- t- Bu substitution pattern emerged as a hit with MIC levels ≤2 μg/mL across four strains of MRSA. In addition, the same compound proved highly potent against Enterococcus spp. (0.25 μg/mL).

Quinoline Hydrazide/Hydrazone Derivatives: Recent Insights on Antibacterial Activity and Mechanism of Action

“…[49] Figure 10. 4-Substituted aryl quinoline hydrazide/hydrazone derivatives (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). Metwally et al (2006) prepared and evaluated the hydrazones derivatives of 2-aryl-quinoline-4-carboxylic acid for antibacterial activity.…”

“…Quinoline derivatives exhibited various pharmacological activities viz . anti‐inflammatory, [17–22] anticancer, [23–25] antihypertensive, [26–29] tyro kinase PDGF‐RTK‐inhibition, [30,31] anti‐HIV, [32–34] antimalarial [35–39] and antimicrobial [40–45] …”

“…anti-inflammatory, [17][18][19][20][21][22] anticancer, [23][24][25] antihypertensive, [26][27][28][29] tyro kinase PDGF-RTK-inhibition, [30,31] anti-HIV, [32][33][34] antimalarial [35][36][37][38][39] and antimicrobial. [40][41][42][43][44][45] Quinoline derivatives inhibit the DNA gyrase (topoisomerase II) activity. DNA gyrase enzyme helps to cut the DNA and causes supercoiling.…”

Synthesis, structural characterization and antibacterial activity evaluation of novel quinolone-1,2,3-triazole-benzimidazole hybrids

“…2-Quinolones and their analogues are important nitrogen-containing heterocycles, widely present in nature as alkaloids (such as Viridicatol or Viridicatin (Fig. 1)) [5][6][7][8] and possess an extensive spectrum of biological properties among which is the antimicrobial [9,10]. Many of the quinolone-based scaffolds with antibacterial activity, were found to act mainly by inhibiting the activity of bacteria type II topoisomerase (DNA gyrase) or type IV topoisomerase [11].…”