Development of Quinoline-Based Disruptors of Biofilm Formation Against Vibrio cholerae

Abstract

Biofilm formation is a major cause of bacterial persistence in nosocomial infections, leading to extended treatment times and increased rates of morbidity and mortality. Despite this, there are currently no biofilm inhibitors approved for clinical use. The synthesis and biological evaluation of a library of amino alcohol quinolines as lead compounds for the disruption of biofilm formation in Vibrio cholerae is now reported. Application of selective metal-halogen exchange chemistry installed both stereocenters in one step, to afford a simpler scaffold than the initial lead molecule, with an EC50 < 10 μM.

Living in the matrix: assembly and control of Vibrio cholerae biofilms

“…Coupling this technique with cellular viability measurements permits the differentiation of bactericidal agents and compounds that selectively disrupt biofilm formation without affecting cell survival. Using this approach, two novel scaffolds have been reported: the natural product oxazine and a quinoline-based molecule (unnamed) 123,124 . In both cases, the authors have developed strategies for the synthesis of libraries of analogues of these compounds to determine the structural features required for biofilm inhibition and to develop synthetic analogues with improved potencies compared with the original lead compounds 123,125 .…”

Fungal Endosymbionts of Macroalgae: Need for Enquiries into Diversity and Technological Potential

“…Bioactivity profiles can also help overcome the issue relating to redundant results where bioactivity against selected human pathogens is the primary method of screening for potential novel compounds when testing crude extracts and fractions from FEMs. By creating a profile of extract activity against a large number of bacteria and comparing this to the activities of known antibiotics where the mode of action has been characterized [30,31], it would be possible to focus efforts on unique crude extracts containing potentially novel metabolites.…”

Convergent Synthesis of 2-Aryl-Substituted Quinolines by Gold-Catalyzed Cascade Reaction

“…[5][6][7] Therefore, quinoline compounds have inspired the development of new synthetic methods 8,9) for the formation of the N-heterocyclic scaffold due to their potential utility in the pharmaceutical industry. As classical and conventional synthetic methods, the Skraup,10) Doebner and von Miller, 11) Combes, 12) Friedländer, 13) and Pfitzinger 14) quinoline syntheses are well known; however, these methods often encounter problems with functional group compatibility as they require strong acidic or basic conditions.…”