This research aimed to prepare novel furyl-2-carboxamide derivatives and to evaluate their in-vitro antiproliferative using MTT assay test for human colorectal cell line (HCT-116) as anticancer activity in multiple concentration dilution. Most of these compounds were prepared adopting the direct coupling of the 2-furyl chloride with the correspondent amines in 1,4-dioxane, DMSO, DMF or CHCl3 with or without a base catalyst. Alternatively, direct fusion method was utilized with some groups giving better yields. Most compounds were obtained in a reasonable yield and their structures were confirmed by Nuclear magnetic resonance spectra (NMR), Fourier transform infrared spectroscopy (FTIR), High resolution mass spectra (HRMS), then evaluated in-vitro with MTT assay test by three trials for each ligand 3, 5, and 7 with Doxorubicin (as a reference drug), the three ligands showed significant moderate and almost identical cellular growth inhibitory activity against human carcinoma colon HCT-116 cell line, in the examined concentration range (0.01-100 ?M). The highest growth inhibitory activity against colon cancer cells is shown by ligand 3, which contains the anthraquinone core structure similar to Doxorubicin, with GI50 value of 23.3 ?M, followed by ligand 7, containing pyridine moiety, and ligand 5, containing benzophenone structure, with GI50 values of 30.5 ?M and 36.6 ?M, respectively. The results indicate that the anthraquinone ligand 3 is 1.3-1.6 times more potent against human colon cancer HCT-116 cells, than the pyridine and benzophenone ligands 7 and 5, respectively.