Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization

Abstract

A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts.

Reactivity of 4H-3,1-benzoxazin-4-ones towards nitrogen and carbon nucleophilic reagents: applications to the synthesis of new Heterocycles

“…They are indeed useful intermediates in organic synthesis affording through reaction with nitrogen nucleophiles 4(3H)quinazolinones. With the aim of extending information on the reactivity of 4H-3,1-benzoxazinones and also synthesizing from them new heterocyclic systems, potentially with biological activity [8][9][10][11][12] and in continuation of our work on the behaviour of stable benzoxazinones 13 towards nitrogen and carbon nucleophiles, other derivatives were obtained via the interaction of acetic anhydride and/or isobutyroyl chloride with anthranilic acid derivatives. The electronically unsaturated character of unstable benzoxazinones which are (4H)-3,1-benzoxazinones bearing saturated substituents such as CH 3 , CH 2 COCH 3 , CH 2 CN and CH 2 CH 2 CO 2 H at position 2 [14][15][16][17] renders their synthesis difficult because they are not satisfactorily stable rings.…”

Unusual saccharin-N,O (carbonyl) coordination in mixed-ligand copper(II) complexes: Synthesis, X-ray crystallography and biological activity

“…thus reaching the site of action more efficiently [52]. Furthermore, by being smaller in size, the steric hindrance is reduced thus allowing the complex to be more effective in entering the cells and causing cell death [53].…”

Synthesis and Photophysical Property Studies of the 2,6,8-Triaryl-4-(phenylethynyl)quinazolines

“…A series of the analogous 2,3-disubstituted 6,8-dibromoquinazolin-4(3H)-ones have been prepared before via the reaction of 6,8-dibromo-2-methyl-1-benzoxazin-4(3H)-one with nitrogen nucleophiles such as hydrazine hydrate, sulpha drugs and 4-aminoacetophenone [19]. Likewise, the 6-fluoro-8-iodo/bromo-2-methyl-1-benzoxazin-4(3H)-ones reacted with aqueous ammonia under reflux to yield the 6-fluoro-8-(iodo/bromo)-2-methylquinazolin-4(3H)-ones [20]. …”