EVALUATION OF THE ANTITUMOR AND CHEMOPREVENTIVE POTENTIAL OF CINNAMOYL-BASED COMPOUNDS

Abstract

Trans-cinnamaldehye occurs naturally in cinnamon bark, and exhibits biological activities, which include antiproliferative and cytoprotective effects. Novel analogs of cinnamaldehyde synthesized to improve the pharmacophore potency were evaluated for antitumor and cancer preventive properties. Mechanisms underlying these properties were also investigated. Novel analogs outperformed cinnamaldehyde in their anticancer and cytoprotective activities. While cinnamaldehydes induced apoptosis in cancer cells by induction of G2 phase arrest and tubulin aggregation, their cytoprotective actions were mediated by induction of phase 2 enzymes via stabilization of the transcription factor Nrf2. A novel group of compounds, supercinnamaldehydes, were also screened for cytoprotective and anti-inflammatory activities to evaluate their cancer preventive actions. Cytoprotective and anti-inflammatory activities were found to be correlated, and an analog HLO6 emerged as the most potent among the series. Based on these results, the cinnamaldehyde pharmacophore represents a promising scaffold that can be tailored to design future therapeutics for cancer therapy and prevention.