Synthesis and evaluation of a series of caffeic acid derivatives as anticancer agents

Abstract

Context: Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, the zinc-dependent endopeptidases involved in the degradation of extracellular matrix (ECM) and releasing growth factors and cytokines residing in ECM. Amongst 23 types of MMPs, an isomer called MMP-9 has been found to play a vital role in angiogenesis, and its overexpression leads to cancer. Inhibition of MMP-9 could be very useful for the treatment of cancer. Objectives: The present work consists of design, synthesis and cell viability assay of a series of caffeic acid derivatives as anticancer agents. Methods: A convergent method was followed in order to synthesize caffeic acid derivatives using microwave assisted synthesis. All the synthesized compounds were studied by docking to determine the binding interactions for the best fit conformations in the binding site of MMP-9 protein and based the docking results, seven compounds were evaluated as anticancer agents by in vitro cell viability assay. Results: Compounds 2, 4, 8, 9, 14, 15 and 21 showed inspiring interactions with MMP-9 enzyme in silico docking studies. In the in vitro cell viability assay, compound 15 was found as the most potent amongst selected caffeic acid derivatives. Conclusion: These newly designed molecules thus can act as starting hits for the design of new and effective inhibitors of MMP-9 for the potential treatment of cancer. Keywords: Angiogenesis, Anticancer agents, Caffeic acid derivatives, Matrix metalloproteinases, MMP-9 inhibitors