Colorectal carcinoma (CRC) is one of the most often detected tumors of the digestive tract and the leading cause of cancer-related mortality worldwide. The present study demonstrates that synthesis and inhibitory potential of 1,3-thiazin-6-ones in vitro against colorectal cancer cells and investigated the underlying mechanism. The study revealed that 1,3-thiazin-6-one effectively targets proliferation potential of HT-29 and HCT116 cells and markedly reduced colony formation capacities without any harmful effect on NCM460 normal cells. Transwell assay showed that 1,3-thiazin-6-one treatment at 32 mu M markedly suppressed invasion potential of HT-29 and HCT116 cells. It was observed that 1,3-thiazin-6-one treatment could markedly reduce NRP2 expression in HT-29 and HCT116 cells. It was also observed that the expression level of E-cadherin was significantly increased while the levels of N-cadherin and Vimentin were significantly decreased by 1,3-thiazin-6-one treatment in HT-29 and HCT116 cells. In silico data using AutoDock vina and Discovery Studio software revealed that 1,3-thiazin-6-one binds to NRP2 and vimentin proteins with binding affinity of -6.5 and -7.4 kcal/mol, respectively. It was found that vimentin protein binds to 1,3-thiazin-6-one through LEU (D:393), ILE (C:397), ASP (C:394), GLU (D:396), ALA (C:398), and ARG (C:401) amino acid residues. Moreover, the interaction of 1,3-thiazin-6-one with NRP2 protein involves ILE (A:348), ARG (A:421), ARG (A:350), GLN (A:353) and HIS (A:312) amino acid residues. In summary, 1,3-thiazin-6-one inhibited proliferation, colony formation potential and invasiveness of the CRC cells by targeting the expression of NRP2. Moreover, it promoted the expression of E-cadherin and targeted the levels of N-cadherin and Vimentin in HT-29 and HCT116 cells. Thus, 1,3-thiazin-6-one may be developed as a therapeutic agent for the treatment of colorectal cancer.