Application of cinnamic acid in the structural modification of natural products: A review

Natural products can generally exhibit a variety of biological activities, but most show mediocre performance in preliminary activity evaluation. Natural products often require structural modification to obtain promising lead compounds. Cinnamic acid (CA) is readily available and has diverse biological activities and low cytotoxicity. Introducing CA into natural products may improve their performance, enhance biological activity, and reduce toxic side effect. Herein, we aimed to discuss related applications of CA in the structural modification of natural products and provide a theoretical basis for future derivatization and drug development of natural products. Published articles, web databases (PubMed, Science Direct, SCI Finder, and CNKI), and clinical trial websites (https://clinicaltrials.gov/) related to natural products and CA derivatives were included in the discussion. Based on the inclusion criteria, 128 studies were selected and discussed herein. Screening natural products of CA derivatives allowed for classification by their biological activities. The full text is organized according to the biological activities of the derivatives, with the following categories: anti-tumor, neuroprotective, anti-diabetic, anti-microbial, anti-parasitic, anti-oxidative, anti-inflammatory, and other activities. The biological activity of each CA derivative is discussed in detail. Notably, most derivatives exhibited enhanced biological activity and reduced cytotoxicity compared with the lead compound. CA has various advantages and can be widely used in the synthesis of natural product derivatives to enhance the properties of drug candidates or lead compounds.