Novel antiviral benzofuran-transition metal complexes

(5-(1H-benzo[d]imidazol-2-yl)-1H-pyrrol-3-yl)(6-hydroxy-4,7-dimethoxybenzofuran-5-yl)methanone (4) and 3-(6-hydroxy-4,7-dimethoxybenzofuran-5-carbonyl)-6H-pyrimido[1,6-a]pyrimidine-6,8(7H)-dione (5) were synthesized by the reaction of 4,7-dimethoxy-5-oxo-5H-furo[3,2-g]chromene-6-carbaldehyde (1) with (1H-benzo[d]imidazol-2-yl)methanamine dihydrochloride and 4-amino-2,6-dihydroxypyrimidine, respectively, via ROR in the presence of alcoholic KOH. The metal complexes 6-9 of compound 4; H2L1 with (CuCl2, FeCl3, ZnCl2, and LaCl3) and the metal complexes 10-13 of compound 5; H2L2 with (CuCl2, FeCl3, CoCl2 and LaCl3) were synthesized to form 1:1 or 1:2 (metal: ligand) complexes. The HIV inhibitory activity of all new compounds was tested. The EC50 values showed that, all of tested compounds were more potent than Atevirdine. Moreover, the benzoimidazolylpyrrole derivative 4 (EC50=9 x 10(-6) mu M) had higher therapeutic index than the standard. The HIV-1 RT inhibitory activity showed that all of the tested compounds showed significant potency but none of them showed higher activity than Atevirdine. The HCV NS3-4A protease inhibitor activity of the tested compounds revealed that the complex formation had great positive effect on the bioactivity, where the Fe-complex 7 was the most potent compound with higher therapeutic index than VX-950, the standard. Also, the cytotoxicity of the synthesized compounds on hepatocyte cell line, showed that Cu-complex 10 was the most potent compound with potency nearly to that of the standard. (c) 2010 Elsevier Masson SAS. All rights reserved.