New Library of Iodo-Quinoline Derivatives Obtained by an Alternative Synthetic Pathway and Their Antimicrobial Activity

Abstract

6-Iodo-substituted carboxy-quinolines were obtained using a one-pot, three-component method with trifluoroacetic acid as a catalyst under acidic conditions. Iodo-aniline, pyruvic acid and 22 phenyl-substituted aldehydes (we varied the type and number of radicals) or O-heterocycles, resulting in different electronic effects, were the starting components. This approach offers advantages such as rapid response times, cost-effective catalysts, high product yields and efficient purification procedures. A comprehensive investigation was conducted to examine the impact of aldehyde structure on the synthesis pathway. A library of compounds was obtained and characterized by FT-IR, MS, 1H NMR and 13C NMR spectroscopy and single-ray crystal diffractometry. Their antimicrobial activity against S. epidermidis, K. pneumonie and C. parapsilosis was tested in vitro. The effect of iodo-quinoline derivatives on microbial adhesion, the initial stage of microbial biofilm development, was also investigated. This study suggests that carboxy-quinoline derivatives bearing an iodine atom are interesting scaffolds for the development of novel antimicrobial agents.

Structural Elucidation of a New Puzzling Compound Emerged from Doebner Quinoline Synthesis

“…Interestingly, in the presence of salicylaldehyde, which features an activating electron-donating group (hydroxyl) in the ortho position, compound 4 turned up as the primary product, accompanied by 2-methyl-4carboxyquinoline (5) as a by-product (Scheme 1). The formation of by-product 5 was consistent across different starting aldehydes, as reported previously [36]; however, compound 4 was something that we never encountered in our previous synthetic attempts. Going further, we reacted para-hydroxyl benzaldehyde with para-iodine aniline while keeping the rest of the experimental conditions constant and obtained the expected quinoline derivative.…”

“…The compound described in this study emerged during our attempts to synthesize new quinoline derivatives by reacting para-iodine aniline with various substituted aldehydes using an extended version of the Doebner reaction, wherein acetic acid served as the reaction medium [36]. Interestingly, in the presence of salicylaldehyde, which features an activating electron-donating group (hydroxyl) in the ortho position, compound 4 turned up as the primary product, accompanied by 2-methyl-4carboxyquinoline (5) as a by-product (Scheme 1).…”

“…It also has correlations with carbon atoms situated two (C3 (133.6 ppm) and C5 (138.9 ppm)) and three (C15 (110.6 ppm)) bonds apart, visible in the H,C-HMBC spectrum (Figure 4). As in our previous attempts to obtain quinoline derivatives using Doebner-type reaction conditions, we obtained pyrrol-2-one derivatives as by-products [36]; we looked into the possibility that our unknown compound also contained this ring. Indeed, we identified in the proton-carbon and proton-nitrogen HMBC spectra several correlations that enabled us to find and assign all the carbons and nitrogen atoms belonging to the pyrrol-2-one residue (ring D).…”

“…In the same study, we showed that all the newly synthesized quinoline derivatives demonstrated good activity against S. epidermidis and C. parapsilosis. Due to their hydrophobic nature, these derivatives can easily penetrate the stratum corneum, increasing their bioavailability for skin infection [36].…”