Solvatochromic fluorophores based on 6-fluoro-2-(aryl)quinoline-4-carboxylic acids: synthesis, optical studies and evaluation of their antimicrobial and larvicidal properties

Abstract

6-Fluoro-2-(aryl)quinoline-4-carboxylic acids 1–11 were synthesized via Pfitzinger reactions between 5-fluoroisatin and methyl aryl ketones. The molecules were studied regarding the impact of their substituent patterns (a-e) on their optical and bioactivity properties. All compounds were fluorescent in solution and had significant solvatochromic behavior, measured in tetrahydrofuran, dichloromethane, dimethylsulfoxide, acetonitrile, methanol, and water at different pHs. Compounds emitted in a broad spectral range from ultraviolet to green, with quantum efficiencies, varying from very weak (ex.: <0.5 % for 1a in DMSO and MeOH) to moderate-strong (∼35 % for 11e in dichloromethane). A biomonitoring of the synthetized compounds reveals antimicrobial and larvicidal (Aedes aegypti mosquitoes) profile. Gram-positive bacterial and fungal species showed greater sensitivity to the 11e, that presented both bactericidal and fungicidal nature. This compound with a methylenedioxy substituent showed favourable interactions with Dehydrosqualene synthase (DQS) and Squalene synthase (SQS), well-validated antimicrobial targets, considering key residues in the complex formation. The molecule also presented a good larvicidal profile, ranking second in terms of significant LC50 values. Thus, 11e has demonstrated an advantage scaffold for future biological tests in other organisms or at the cellular level.