title: Biological activity of some 4-anilinoquinazolines: cytotoxic, genotoxic and antiprotease effects, induction of necrosis and changes of actin cytoskeleton.
abstract: Fourteen substituted 4-anilinoquinazolines have been tested for cytotoxic effect and structure activity relationships. The most active derivatives were substituted by chlorine or bromine group in the aromatic ring, in the pyrimidine ring by morpholine group and in the aniline skeleton by nitro group in position 4 or 2. Derivatives 6-bromo-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline, 6-bromo-2-morpholin-1-yl)-4-anilinoquinazoline, 2-(morpholin-1-yl)-4-(4'-bromoanilino)-quinazoline and 6-chloro-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline inhibited growth of tumor cell lines HeLa, B16 and L1210. Mutagenic data provided by Ames test showed, that the compounds 6-bromo-2-morpholin-1-yl)-4-anilinoquinazoline and 2-(morpholin-1-yl)- 4-(4'-bromoanilino)quinazoline did not exhibit the mutagenic effect, whereas the compounds 6-bromo-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline and 6-chloro-2-(morpholin-1-yl)-4-(4'-nitroanilino) quinazoline increased slightly the number of revertants of the strain TA 98 without metabolic activation. Concentration 26 micromol/L of 6-bromo-2-(morpholin-1-yl)-4-anilinoquinazoline induced necrosis of tumor cells B16. Concentration 5.2 micromol/l induced a significant increase of filamentous actin in the transformed HepG2 cells. Derivatives 6-bromo-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline, 6-bromo-2-morpholin-1-yl)-4-anilinoquinazoline, 2-(morpholin-1-yl)-4-(4'-bromoanilino)quinazoline and 6-chloro-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline exhibited antiprotease effect on plasmine. This results could be relevant for the anticancer properties of these compounds.
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Chemical Technology, Slovak University of Technology, Bratislava, Slovak Republic. jantova@chtf.stuba.sk
authors.forename: S
authors.initials: S
authors.lastname: Jantová
authors.forename: M
authors.initials: M
authors.lastname: Urbancíková
authors.forename: T
authors.initials: T
authors.lastname: Maliar
authors.forename: M
authors.initials: M
authors.lastname: Mikulásová
authors.forename: P
authors.initials: P
authors.lastname: Rauko
authors.forename: L
authors.initials: L
authors.lastname: Cipák
authors.forename: J
authors.initials: J
authors.lastname: Kubíková
authors.forename: S
authors.initials: S
authors.lastname: Stankovský
authors.forename: K
authors.initials: K
authors.lastname: Spirková
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000473:pathology; D008545:Melanoma / Q000473:pathology; D051379:Mice; D009152:Mutagenicity Tests; D009336:Necrosis; D011480:Protease Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
chemical_list: D011480:Protease Inhibitors; D011799:Quinazolines