Identification of benzofuro[2,3-b]quinoline derivatives as a new class of antituberculosis agents

A series of 11-alkoxylated and 11-aminated benzofuro[2,3-b]quinoline derivatives were designed, synthesized, and evaluated for their anti-TB and cytotoxic activities. The known 11-chlorobenzofuro[2,3-b]quinoline (3) was synthesized in a single step from anthranilic acid and 2-coumaranone in phosphorus oxychloride in 51% yield for the first time. Treatment of 3 with alcohols and amines gave 11-alkoxylated and 11-aminated benzofuro[2,3-b]quinoline derivatives respectively, which were evaluated for their anti-TB and cytotoxic activities. Our results indicated that 11-arylaminated derivatives were more active than their respective 11-aryloxylated isosteric isomers against Mycobacterium tuberculosis. Among the tested compounds, 11-methoxybenzofuro[2,3-b]quinoline (4), 11-methylamino- benzofuro[2,3-b]quinoline (9), and 11-dimethylaminobenzofuro[2,3-b]quinoline (14) exhibited significant activities against the growth of M. tuberculosis (MIC values of <0.20 μg/mL) and low cytotoxicities against VERO cell with IC50 values of 11.77, 5.55, and >30.00 μg/mL respectively. The selectivity index (SI = IC50/MIC) for 4, 9, and 14 was greater than 58.85, 27.75, and 150 respectively.

Graphical abstractCompounds 4, 9, and 14 exhibited significant activities against the growth of M. tuberculosis with a selectivity index (SI) of greater than 58, 27, and 150 respectively.Figure optionsDownload full-size imageDownload as PowerPoint slide