Synthesis, antidepressant and antifungal evaluation of novel 2-chloro-8-methylquinoline amine derivatives

A new series of N-[(2-chloro-8-methylquinolin-3-yl)methyl]-(substituted)-aniline/butylamine/cyclohexylamine/benzylamine derivatives (4a–p) was synthesized by nucleophilic substitution reaction of 2-chloro-3-(chloromethyl)-8-methylquinoline 3 with various aliphatic and aromatic amines in absolute ethanol in the presence of triethylamine (TEA). The newly synthesized secondary amines were characterized by the combined use of IR, 1H NMR, 13C NMR, mass spectral data and microanalyses. The antidepressant activity of the synthesized compounds (4a–p) was evaluated by Forced swim test in rats and their neurotoxicity was evaluated by the rotarod test. Test compounds and clomipramine were administered intraperitoneally at dose of 100 mg/kg and 20 mg/kg respectively. Preliminary antidepressant screening of compounds (4a–p) revealed that compounds 4b, 4c, 4d, 4e, 4i and 4o significantly (P < 0.01) reduces the duration of immobility time. These compounds were also tested in-vitro for MAO inhibitory effect. All the compounds were also screened for antifungal activity against Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277, Monascus purpureus MTCC 369 and Penicillium citrinum NCIM 768 strains.

A series of heteroaryl amines containing 2-chloro-8-methylquinoline derivatives were synthesized and evaluated for antidepressant and antifungal activity.Figure optionsDownload as PowerPoint slideResearch highlights
► Our research manuscript highlight the design and development of quinoline based heteroaryl amines as antidepressant and antifungal agent.
► The analogue was designed based on the fact that Quipazine a quinoline derivative has shown promising antidepressant activity.
► Some of the compounds emerged as most potential antifungal and antidepressant agents but the purposeful modification of compounds did not produce any significant enhancement in MAO inhibitory activity as expected.
► These finding suggest a different mechanism of action of these compounds beside inhibition of MAO.