Impact of Alkyl Esters of Caffeic and Ferulic Acids on Tumor Cell Proliferation, Cyclooxygenase Enzyme, and Lipid Peroxidation

Abstract

The antioxidant ferulic and caffeic acid phenolics are ubiquitous in plants and abundant in fruits and vegetables. We have synthesized a series of ferulic and caffeic acid esters and tested for tumor cell proliferation, cyclooxygenase enzymes (COX-1 and -2) and lipid peroxidation inhibitory activities in vitro. In the tumor cell proliferation assay, some of these esters showed excellent growth inhibition of colon cancer cells. Among the phenolics esters assayed, compounds 10 (C12-caffeate), 11 (C16-caffeate), 21 (C8-ferulate), and 23 (C12-ferulate) showed strong growth inhibition with IC50 values of 16.55, 13.46, 18.67, and 7.57 microg/mL in a breast cancer cell line; 9.65, 7.45, 17.05, and 4.35 microg/ mL in a lung cancer cell line; 5.78, 3.5, 4.29, and 2.46 microg/mL in a colon cancer cell line; 12.04, 12.21, 14.63, and 8.09 microg/ mL in a central nervous system cancer cell line; and 8.62, 7.76, 11.0, and 5.37 in a gastric cancer cell line. In COX enzyme inhibitory assays, ferulic and caffeic acid esters significantly inhibited both COX-1 and COX-2 enzymes. Caffeates 5-10 (C4-C12), inhibited COX-1 enzyme between 50% and 90% and COX-2 enzyme by about 70%, whereas ferulates 15-21 (C3-C8) inhibited COX-1 and COX-2 enzymes by 85-95% 25 microg/mL. Long-chain caffeates 11-14 (C16-C22) and short-chain ferulates 15-20 (C3-C5) were the most active in lipid peroxidation inhibition and showed 60-70% activity at 5 microg/mL concentration.

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

“…Caffeic acid and some of its esters and amides derivatives exhibit a broad spectrum of biological activities including anti-inflammatory [7], antimicrobial [8,9], antioxidant [10], anti-Alzheimer [11], analgesic [12] and anticancer effects [13][14][15]. In addition, some studies have shown that caffeic acid esters have high anti-leishmanial activity [16][17][18][19].…”

Synthesis and leishmanicidal activity of cinnamic acid esters: structure–activity relationship

“…Caffeic acid (1), 3,4-dihydroxy cinnamic acid, and its esters derivatives exhibit a broad spectrum of biological activities, including anti-inflammatory (Jayaprakasam et al, 2006;Da Cunha et al, 2004), antimicrobial (Almajano et al, 2007;Noriaki et al, 2005;King et al,1999;Valenta et al, 1998;Bowles et al, 1994) antioxidant (Hung et al, 2005;Noriaki et al, 2005;Kikuzaki et al,. 2002;Son et al, 2002;Rajan et al, 2001) and anticarcinogenic effects (De et.…”

Dietary Cooked Navy Beans and Their Fractions Attenuate Colon Carcinogenesis in Azoxymethane-InducedOb/ObMice

“…These components include saponins (24)(25)(26); monosaccharides, disaccharides, and oligosaccharides (27); and the phenolic components ferulic acid (28,29), p-coumaric acid (30), kaempferol (31), phytate (32,33), and at smaller concentrations, catechins (34), anthocyanidins (35), and isoflavonoids (36). All of these components are primarily in aqueous-alcohol extracts of dry beans (37)(38)(39)(40).…”