Synthesis, cytostatic evaluation and structure activity relationships of novel bis-indolylmethanes and their corresponding tetrahydroindolocarbazoles.

Abstract BIMs (bis-indolylmethanes) ( 1 a–n ) were synthesized using glacial acetic acid as a protic acid for promotion of the condensation reaction of indoles with aldehydes in high yields (86–98 %). Corresponding tetrahydroindolo[2,3- b ]carbazoles ( 2 a–m ) were synthesized via condensation of BIMs with aldehydes. Ten synthesized compounds have been submitted to the national cancer institute in the USA where all the submitted samples have been selected for one dose screening . As a result of the one dose screening of BIMs ( 1 e,f,h,i,n ) and of the indolocarbazoles ( 2 e,f,h,i,j ) the average highest cytostatic effects was recorded here for the BIM 1 h and the indolocarbazole ( 2 e ) that showed the lowest mean values of “47.39%” and of “21.63%” respectively. Both compounds ( 1 h and 2 e ) were further tested in five dose screening with the tested substance ( 1 h ) being significantly more sensitive for several cancers cell line as corresponding to their GI 50 values. Furthermore, the basically substituted derivative 2 e showed the highest antipoliferative activity in a nanomolar scale towards the three selected cancers cell lines Non small lung cell NCI–H460 with GI 50 “616 nM”, Ovarian Cancer cell line OVCAR-4 with GI 50 “562 nM” and Breast Cancer cell line MCF7 with GI 50 “930 nM”.