Biological activity of some 4-anilinoquinazolines: cytotoxic, genotoxic and antiprotease effects, induction of necrosis and changes of actin cytoskeleton

Fourteen substituted 4-anilinoquinazolines have been tested for cytotoxic e ffect and structure activity relationships. The most active derivatives wer e substituted by chlorine or bromine group in the aromatic ring, in the pyr imidine 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'-nitroanil ino)quinazoline, 6-bromo-2-(morpholin-1-yl)-4-anilinoquinazoline, 2-(morpho lin-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 th e compounds 6-bromo-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline and 6 -chloro-2-(morpholin-1-yl)-4-(4'-nitroanilino) quinazoline increased slight ly the number of revertants of the strain TA 98 without metabolic activatio n. Concentration 26 mu mol/L of 6-bromo-2-(morpholin-1-yl)-4-anilinoquinazo line induced necrosis of tumor cells B16. Concentration 5.2 mu mol/l induce d a significant increase of filamentous actin in the transformed HepG2 cell s. 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'- b romoanilino)quinazoline and 6-chloro-2-(morpholin-1-yl)-4-(4'-nitroanilino) quinazoline exhibited antiprotease effect on plasmine. This results could b e relevant for the anticancer properties of these compounds.