DHFR and breast carcinoma: The derivative 88 which contains (R1= Cl; Ar = 4-BrC6H4) proved to be the most active DHFR inhibitor with an IC50 of 0.06 μM and showed 31.4, 25.2, 37.7, 25.1 and 41.0 GI% against NCI-H522 non-small cell lung, HT29 colon, SK-OV-3 ovarian, MCF7 breast and T-47D breast cancers, respectively.