Novel Cyanoacrylamides Incorporating Sulfamethoxazole as Potential Anticancer Agents: DNA Interaction, Apoptotic Induction, and S-Phase Cell Cycle Arrest in Colon Cancer Cells

In the current study, five novel cyanoacrylamides incorporating sulfamethoxazole (5–9) were designed and synthesized as potential candidates for anticancer therapy. The antitumor potential of the synthesized compounds was screened against HCT116, MDA-MB-231, and A549 human tumor cells. Compound 9, incorporating the 4-(piperidin-1-yl)phenyl moiety, was more effective than 5-fluorouracil against the three cell lines. The shape of colon cancer cells was examined by scanning electron microscope (SEM). Compound 9 could effectively induce HCT116 apoptosis through the remarkable upregulation of Bax and caspase-3 and the downregulation of Bcl2 and survivin. It can also inhibit HCT116 cell cycle progression at the S phase and cell migration, as it significantly downregulates cyclin A1 and upregulates CDH1, respectively. According to UV–vis and EB-displacement measurements, compound 9 could interact with CT-DNA in a mild intercalative way. DNA fragmentation propensities of compound 9 were examined on pBR322 plasmid DNA using gel electrophoresis, revealing that compound 9 exhibited remarkable photofragmentation activity. Moreover, the molecular docking supported that compound 9 had good binding affinities toward the active sites of key proteins implicated in carcinogenesis and metastasis. In conclusion, compound 9 is presented as a remarkable molecule for the development of novel anticancer drugs.