Synthesis and screening of quinolone antibiotic isosteres

Abstract

Condensation of either 4-(benzothiazol-2-yl)phenylamine 1 or 4-amino-2-(benzothiazol-2-yl)-phenol 2 with ethyl cyanoethoxyacrylate or diethyl ethoxymethylenemalonate (EMME) followed by intra molecular thermal cyclisation results in substituted quinolones which upon alkylation then base-hydrolysis yielded the target compounds 6-(benzothiazol-2-yl)-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (3a,b); 7-(benzothiazol-2-yl)-1-alkyl-4-oxo-1,4-dihydro-6-alkoxyquinoline-3-carboxylic acid (4a,b). Meanwhile diazotisation of 4-(benzothiazol-2-yl)phenylamine (1) followed by reaction with malononitrile then intra molecular Friedel-Crafts acylation gave 4-amino-6-(benzothiazol-2-yl)cinnoline-3-carbonitrlie 5. The antimicrobial activity of some of the target compounds using gram-positive microbes (Staphylococcus aureus and Bacillus subtilis) and gram-negative bacteria (‘Escherichia coli and Pseudomonas aeruginosa) is carried out and 6-(benzothiazol-2-yl)-1-alkyl-4-oxo-1,4-dihydro quinoline-3-carboxylic acid (3a,b) and 7-(benzothiazol-2-yl)-1-alkyl-4-oxo-1,4-dihydro-6-alkoxyquinoline-3-carboxylic acid (4a,b) showed promising activity.