title: The novel [4,5-e][1,3]diazepine-4,8-dione and acyclic carbamoyl imino-ureido derivatives of imidazole: synthesis, anti-viral and anti-tumor Activity evaluations.
abstract: In the present paper, we report on the synthesis, and in vitro antiviral and cytostatic activities of a series of novel imidazole[4,5-e][1,3]diazepine-4,8-dione (compounds 9-11) and acyclic carbamoyl imino-ureido imidazole (compounds 12 and 13) derivatives. These new type of chemical entities showed no significant activity on the broad spectrum of DNA and RNA viruses. Results of antiproliferative assays performed on a panel of selected human tumor cell lines revealed that only compounds 1 and 5 showed moderate and selective cytostatic effect against HeLa cells (IC50 = 24 and 32 µM) with no concomitant cytotoxic effects on human normal fibroblasts (BJ). Importantly, an imidazole derivative containing a pyrrolidine moiety linked via an ethylenic spacer (3) showed a selective cytostatic effect toward cervical carcinoma (HeLa) cells (IC50 = 9.5 µM) with no apparent cytotoxicity on human normal fibroblasts (BJ). This compound can be therefore considered as a potential anti-tumor lead compound for further synthetic structure optimization.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, Zagreb HR-10000, Croatia. mmintas@fkit.hr.
authors.forename: Karlo
authors.initials: K
authors.lastname: Wittine
authors.forename: Kristina
authors.initials: K
authors.lastname: Poljak
authors.forename: Matea
authors.initials: M
authors.lastname: Kovač
authors.forename: Damjan
authors.initials: D
authors.lastname: Makuc
authors.forename: Janez
authors.initials: J
authors.lastname: Plavec
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Tamara
authors.initials: T
authors.lastname: Martinović
authors.forename: Sandra Kraljević
authors.initials: SK
authors.lastname: Pavelić
authors.forename: Krešimir
authors.initials: K
authors.lastname: Pavelić
authors.forename: Mladen
authors.initials: M
authors.lastname: Mintas
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004267:DNA Viruses / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007093:Imidazoles; C029899:imidazole