Abstract:
Due to the emerging mortality rate of colorectal cancer there is a high need for the management and control of
this disease. Although several treatment approaches are being developed day by day yet the high incidence rate of
colorectal cancer is still not controlled. To ease in the development of treatment therapies for colorectal cancer two
derivatives of ethyl 2-aminothiazole 4-carboxylate were designed and synthesized. The compounds Ethyl 2-(2-(1,3-
dioxoisoindolin-2-yl)acetamido)thiazole-4-carboxylate (5a) and ethyl 2-(2-(1,3-dioxoisoindolin-2-yl)-3-
phenylpropanamido)thiazole-4-carboxylate (5b) were characterized and studied for their anti-cancer activities. The in
silico molecular modeling studies were performed against the target protein beta-catenin which is an important player in
the progression of colorectal cancer. The in silico ADMET studies were performed to assess the basic physicochemical
properties of these compounds. The in vitro antiproliferative assay and the enzyme inhibitory assay was performed to
validate the role of these compounds in the colorectal cancer. The preliminary cytotoxic assay and the MTT assay of the
compounds 5a and 5b against the colorectal cancer cell line HCT 116 showed 60% inhibition of cell proliferation with
IC50 of 0.72µM and 1.55µM, respectively. The standard methotrexate showed IC50 of 0.7µM showing potent inhibitory
action of these compounds. The in vitro validation of the anti-cancer effect of both compounds revealed significant
inhibition of beta-catenin concentration at higher doses as compared to control. Both the in vitro and in vivo assays of
compounds showed effective anti-cancer activities and depicts the future potential of these compounds in colorectal
cancer.
