Synthesis of thieno[2,3-b]benzo[1,8]naphthyridine-2-carboxylic acids under microwave irradiation and interaction with DNA studies

Abstract

The microwave-enhanced synthesis of 2-chloro-3-formylbenzo(1,8)naphthyridines 3a-c has been achieved rapidly in good yield via the Vilsmeier-Haack cyclisation of N-(4-methylquinolin-2- yl)acetamide 2a-d. The precursors N-(4-methylquinolin-2-yl)acetamide derivatives were effectively prepared in a single step from 2-aminoquinoline and acetic anhydride in presence of Amberlite-120A cation exchange catalyst under microwave irradiation. Condensation of 3a-d, with thioglycolic acid under microwave irradiation using anhydrous potassium carbonate as catalyst afforded thieno(2,3-b)benzo(1,8)naphthyridine-2-carboxylic acids (TBNCS) 4a-g. Elemental analysis, IR, 1 H NMR, and mass spectral studies were used to characterize these compounds. The interaction of thieno(2,3-b)benzo(1,8)naphthyridine-2-carboxylic acid (TBNC) (4a) with CT-DNA was studied by UV-Vis, viscosity as well as thermal denaturation methods. On binding to DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. Binding parameters, determined from spectrophotometeric measurements indicated a binding constant of 1.8 X 10 6 M -1 . The thieno(2,3-b)benzo(1,8)naphthyridine-2-carboxylic acid (4a) increases the viscosity of sonicated rod-like DNA fragments. The binding of TBNC to DNA increased the melting temperature by about 4 0 C. DNA interaction studies suggest that (4a) binds to calf thymus DNA (CT-DNA).