synthesis, characterization and evaluation of anticancer activity of some 6-(chloro/methoxy/methyl)-𝑁-(4-substitutedphenyl)-4-thiomorpholinoquinazolin-3(4𝐻)-amine derivatives

Among the many nitrogen heterocycles investigated for pharmaceutically significant compounds, quinazolines have garnered significant attention due to their broad spectrum of biological activity. a set of twelve quinazoline analogues were synthesized specifically 6-(chloro/methoxy/methyl)-n-(4-substitutedphenyl)-4-thiomorpholinoquinazolin-3(4h)-amine derivatives. the spectral analysis has confirmed the structures of the compounds. the cytotoxicity of the synthesized compounds was assessed against five cancer cell lines (breast- (mcf7 mda-mb-231), kidney- (hek-293), nih/3t3- (mouse embryonic fibroblast), and lung- (a549) via srb assay at the single dose of 25 μm. the doxorubicin (dox) was chosen as a positive control. it was noticed that compounds (2, 3, 11, 14, 15, and 27) showed % cell viability less than 50% against mcf-7 and hek-293. only two compounds (2 and 11) showed >50 % inhibition at 25 μm concentration against a-549 cells. interestingly, it has been found that all the exhibited >50% inhibition at 25 μm concentration against mda-mb-231 (except 2, 11, and 14) cells. compounds which displayed >50% inhibition at 25 μm concentration were further taken up for gi50 determination. in general, the inclusion of electron withdrawing groups (-no2, -oh) instead of –och3 at the 4th position reduces the anti-cancer effectiveness. in contrast, the presence of an electron donating group (–ch3) at the 4th position on the phenyl ring enhances the activity, with the exception of compound 2. in addition, the inclusion of a bromine (-br) group at the 2nd and 4th positions of the phenyl ring decreases the cytotoxicity. although, the compounds bearing -methyl and -methoxy substitution on phenyl (3 and 11) showed good cytotoxicity against mcf-7 cells from these screening it was concluded that compound 2 (6-(chloro)-3-((4-nitrophenyl) amino)-4-thiomorpholinoquinazolin-3-ium) can be treated as lead nucleus and should be developed further to claim its clinical use for the treatment of cancer.