Novel Cinnamic Acid Derivatives as Potential Anticancer Agents: Synthesis, In Vitro Cytotoxicity and Molecular Docking Studies

Abstract

Inhibition of matrix metalloproteinase-9 (MMP-9) can be an emerging strategy for a cancer cure as overexpression of MMP-9 is associated with several types of malignancies, including cancers related to lungs, breasts, and prostate. The present work was proposed to design and synthesize some novel cinnamic acid derivatives as potential anticancer agents. Novel cinnamic acid derivatives were designed using a structure-based drug design approach, and a series of 16 newer cinnamic acid analogs was prepared and evaluated for in vitro cytotoxicity (lung cancer cell line, A-549), followed by docking studies to explore binding interactions of designed compounds in the binding site of MMP-9. In the in vitro cytotoxicity assay, compound 5 was found to be most potent, with an IC50 value of 10.36 µM amongst the synthesized analogs. The designed molecules showed appreciable docking interactions and binding patterns with MMP-9 protein supporting the in vitro cytotoxicity outcomes. Compound 5 can be further explored as a possible lead molecule to develop potent and selective MMP-9 inhibitors as potential antineoplastic agents.