Novel antiviral benzofuran-transition metal complexes

Abstract

(5-(1 H-benzo[ d]imidazol-2-yl)-1 H-pyrrol-3-yl)(6-hydroxy-4,7-dimethoxybenzofuran-5-yl)methanone (4) and 3-(6-hydroxy-4,7-dimethoxybenzofuran-5-carbonyl)-6 H-pyrimido[1,6- a]pyrimidine-6,8(7 H)-dione (5) were synthesized by the reaction of 4,7-dimethoxy-5-oxo-5 H-furo[3,2- g]chromene-6-carbaldehyde (1) with (1 H-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; H 2L 1 with (CuCl 2, FeCl 3, ZnCl 2, and LaCl 3) and the metal complexes 10-13 of compound 5; H 2L 2 with (CuCl 2, FeCl 3, CoCl 2 and LaCl 3) were synthesized to form 1:1 or 1:2 (metal: ligand) complexes. The HIV inhibitory activity of all new compounds was tested. The EC 50 values showed that, all of tested compounds were more potent than Atevirdine. Moreover, the benzoimidazolylpyrrole derivative 4 (EC 50 = 9 × 10 −6 μM) 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.