Novel substituted 2-aminophenylthiazole derivatives were synthesized via various synthetic pathways. Among which were compounds bearing different side chains attached to the thiazole backbone through occupying C 2 position 2-4, 6, 8-12,and 15-22. Also thiazole derivatives 23-25 bearing substituted pyrimidines were designed to be synthesized. Moreover, we have synthesized iminothiazolyl succinic acid derivatives 5 a and 5 b , fused thiazolothiadiazole analogue 7, as well as, the thiazolopyrimidine derivatives 13 and 14. The newly synthesized compounds were evaluated for their in vitro anticancer activity against human Liver cancer HepG2 and Breast cancer MCF7 cell lines compared to the reference drug Doxorubicin. Compounds 3, 12, 15, 17, 18, 21, 22 and 24 showed significant activity against HepG2 cell lines with IC 50 values ranging from 4.78-11.4 µg/mL. However, compounds 3, 7, 15, 17, 18 and 22 exerted highly potent anticancer activity against MCF7 cell line with IC 50 values ranging from 4.95-10.8 µg/mL.