Design and synthesis of 2-chloroquinoline derivatives as non-azoles antimycotic agents

Abstract

A series of secondary amines (4-19) containing 2-chloroquinoline as lipophilic domain have been synthesized based on the structural requirements essential for allylamine/benzylamine antimycotics by nucleophilic substitution reaction of 3-chloromethyl-2-chloroquinoline 3 with various aliphatic and aromatic amines in absolute ethanol in the presence of triethylamine. Some N-methyl derivatives (20-25) were also synthesized by N-methylation using (CH 3 ) 2 SO 4 /NaH. The structures of newly synthesized compounds were established by the combined use of IR, 1 H-NMR, 13 C-NMR, and Mass spectra. Compounds 4-25 were screened in vitro at conc. of 200 g/ml for their antifungal activity against Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277, Monascus purpureus MTCC 369, and Penicillium citrinum NCIM 768 by cupplate method using Terbinafine as a references drug. Among the secondary amines, compounds 4, 5, 8, 10, 14, and 16 exhibited potential antifungal activity and their corresponding N-methyl (20-25) derivatives also showed further increase in antifungal activity against fungal strain Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277. Compounds 3-chloro-N-[(2-chloroquinolin-3-yl)methyl]-4-fluoro-N-methylaniline (24) and 3,4-dichloro-N-[(2-chloroquinolin-3-yl)methyl]-N-methylaniline (25) were the most potent derivatives of the series.

In-Vitro Antibacterial / Antifungal Screening of 2-Chloroquinoline Scaffold Derivatives

“…The chlorination of compounds (11,12) with SOCl 2 in dry benzene afforded intermediates 3-(chloromethyl)-2-chloroquinoline (17,18) and their successive nucleophilic substitution reaction with sulphanilamide or p-aminophenol in absolute ethanol in the presence of organic base triethylamine (TEA) gave 2-chloroquinolinyl amines (19)(20)(21)(22). While various 1 H-benzimidazol-2-ylsulfanyl)methyl (23)(24)(25)(26) derivatives were prepared by reacting intermediate (17,18) with 2-mercaptobenzimidazole or 2-mercapto-6-nitrobenzimidazole in ethanol in presence of base NaOH.…”

“…The synthesis was further confirmed by mass spectrometry in which molecular ion peak was registered at m/z 347.11 (M + ) and M+2 peak at 349.11 for compound 20. The synthesis of compounds (23)(24)(25)(26) was established by identifying the characteristics -CH 2 S-peak in NMR. In 1 H-NMR spectra of compounds (23-26) the signal due methylene proton of -CH 2 S-group was resonated at δ value 4.69-4.72 integrating for two protons.…”

“…While their corresponding secondary amines of sulphanilamide (19,20) and p-aminophenol (21,22) was comparatively more active in inhibiting the growth of the bacteria (MIC 12.5 to 25 µg/ml). Among the 2-mercaptobenzimidazole derivatives (23)(24)(25)(26), the nitro derivatives were more active against the all the bacterial strains and there MIC was observed in the range of 25-50 µg/ml.…”

“…The quinolinyl amine derivatives of sulphanilamide and p-amniophenol (19)(20)(21)(22) showed antifungal activity in the range of 25-100 µg/ml. The benzimidazole derivatives (23)(24)(25)(26) showed moderate antifungal activity against the test strain C. albicans, A. niger and A. flavus was and there MIC observed at 25 to 50 µg/ml. To understand the mechanism of action underlying activity of most active compound 21, we proceeded to examine the interaction of compound 21 with bacterial DNA gyrase (PDB code: 3G75) [30].…”

Facile one‐pot synthesis of a series of 7‐aryl‐8H‐benzo[h]indeno[1,2‐b]quinoline‐8‐one derivatives catalyzed by cellulose‐based magnetic nanocomposite

“…Due to wide range of biological and pharmaceutical activities as well as synthetic, chemical and industrial applications, quinolines have attracted researcher's attentions. Some of their medicinal properties include anti ‐ cancer, anti ‐ malarial, anti‐inflammatory, anti ‐ asthmatic, anti ‐ pain, anti ‐ bacterial, anti ‐ virus, anti ‐ fungus, cardiovascular and anti ‐ hypersensitive activities . Indenoquinolines are one of the most important groups of quinoline derivatives that have a wide range of medicinal activities such as anticancer, anti ‐ inflammatory, anti ‐ tumour and inhibitor of steroid reductase, etc.…”