Shibinskaya M. Synthesis, biological activity and strucrure-activity relationship of 1H-indol-2,3-dione and 6H-indolo[2,3-b]quinoxaline derivatives

Thesis for Ph.D. degree on speciality 02.00.10 bioorganic chemistry. A.V. Bogatsky Physico-Chemical Institute of the NAS of Ukraine, Odessa, 2011. The work is devoted to the synthesis and study of biological properties of 1H-indole-2,3-dione and 6H-indolo[2,3-b]quinoxaline derivatives. The methods for the synthesis basic derivatives of 1H-indole-2,3-dione, 6H-indolo[2,3-b]quinoxaline, 7H-benzo[c]-indolo[2,3-b]quinoxaline, and 1,2,3,4-tetrahydro-6H-indolo[2,3-b]quinoxaline were developed. It was developed convenient method of aminoalkylation of 1H-indole-2,3-dione and general method of 6-aminoalkylindoloquinoxalines synthesis that allowed to obtain a wide range of corresponding derivatives with high yield. The novel aminoacylhydrazones of 1H-indole-2,3-dione and 1-(2-diethylaminoethyl)-1H-indole-2,3-dione, 6-aminoalkyl-6H-indolo[2,3-b]quinoxalines, basic amides and esters of indoloquinoxaline-6-yl-carboxylic acids, 7-aminoethyl-7H-benzo[c]-indolo[2,3-b]quinoxalines and 6-aminoethyl-1,2,3,4-tetrahydro-6H-indolo[2,3-b]quinoxalines were synthesized. Interaction of synthesized compounds with DNA was investigated using methods of spectrofluorimetry, spectrophotometry and viscosimetry. For the first time is found, that aminoacylhydrazones of 1H-indole-2,3-dione are DNA intercalators. Interferon inducing properties of 1H-indole-2,3-dione aminoacylhydrazones and indoloquinoxaline derivatives were found for the first time too. The highly effective, low toxic antiviral agents and interferon inducers were selected among the indoloquinoxaline derivatives. Keywords: 1H-indole-2,3-dione, 6H-indolo[2,3-b]quinoxaline, 7H-benzo[c]-indolo[2,3-b]quinoxaline, 1,2,3,4-tetrahydro-6H-indolo[2,3-b]quinoxaline, intercalation, DNA, DNA-binders, antiviral activity, interferon-inducing activity.