Novel 2-pyridone Analogs with Anti-cancer Activity: Synthesis, In silico, and In vitro Evaluation

Background: 2-pyridone is frequently used to synthesize and develop new bioactive molecules approved for treating many diseases. The produced compounds play a significant role in inhibiting cancer growth. Objective: Through a molecular docking investigation, we determined the binding affinity of 2-pyridone compounds with the Matrix Metalloproteinase receptor, which allowed us to develop, produce, and test the in vitro anticancer efficacy of those compounds. Methods: 2-pyridones (A1-A12) were synthesized in a multistep process, followed by spectrum analysis to confirm the structure. In silico screening of the synthesized compounds was carried out with the assistance of AutoDock software. Flow cytometry was used on the HT-29 colon cancer cell line to measure A1-A12’s anticancer effect in a lab setting. Results: The enzyme matrix metalloproteinase receptor and A1-A12 interacted unexpectedly during a docking study (MMP3, MMP9 & MMP13). Research has shown a strong affinity for MMP3 receptors for A9, A10, A11, A12, and A4, respectively. Further flow cytometric testing revealed compound A9 (R1) to be highly cytotoxic, with an IC50 value of 20.77 M. The anticancer activity of A9 (R1) against HT-29 colon cancer cell lines was also confirmed by in vitro results. Conclusion: These findings suggested that 2-pyridone compounds have promising therapeutic potential for cancer treatment, and more research on these lead moieties would be advantageous to discovering an effective anticancer drug.