title: Synthesis, cytostatic evaluation and structure activity relationships of novel bis-indolylmethanes and their corresponding tetrahydroindolocarbazoles.
abstract: BIMs (bis-indolylmethanes) (1a-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 (2a-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 (1e,f,h,i,n) and of the indolocarbazoles (2e,f,h,i,j) the average highest cytostatic effects was recorded here for the BIM 1h and the indolocarbazole (2e) that showed the lowest mean values of "47.39%" and of "21.63%" respectively. Both compounds (1h and 2e) were further tested in five dose screening with the tested substance (1h) being significantly more sensitive for several cancers cell line as corresponding to their GI50 values. Furthermore, the basically substituted derivative 2e showed the highest antipoliferative activity in a nanomolar scale towards the three selected cancers cell lines Non small lung cell NCI-H460 with GI50 "616 nM", Ovarian Cancer cell line OVCAR-4 with GI50 "562 nM" and Breast Cancer cell line MCF7 with GI50 "930 nM".
authors.affiliation: Institute of Pharmacy, Martin-Luther University, Research Group of Drug Development and Analysis, Wolfgang- Langenbeck-Straße 4, 06120 Halle, Saale, Germany; Applied Organic Chemistry Department, National Research Centre, Cairo, Egypt. Electronic address: mardia_elsayed2009@yahoo.com.
authors.forename: Mardia T
authors.initials: MT
authors.lastname: El Sayed
authors.affiliation: Natural Compounds Laboratory, National Research Centre, Cairo, Egypt.
authors.forename: Khadiga M
authors.initials: KM
authors.lastname: Ahmed
authors.affiliation: Institute of Pharmacy, Martin-Luther University, Research Group of Drug Development and Analysis, Wolfgang- Langenbeck-Straße 4, 06120 Halle, Saale, Germany.
authors.forename: Kazem
authors.initials: K
authors.lastname: Mahmoud
authors.affiliation: Institute of Pharmacy, Martin-Luther University, Research Group of Drug Development and Analysis, Wolfgang- Langenbeck-Straße 4, 06120 Halle, Saale, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hilgeroth
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D007211:Indoles
keywords: Antipoliferative activity; Bis-indolylmethanes; Five dose screening; Nanomolar scale; One dose screening; Tetrahydroindolo[2,3-b]carbazoles