The antiproliferative activity of xanthohumol (1), a major prenylated chalcone naturally occurring in hops, and its aurone type derivative (Z)-6,4′-dihydroxy-4-methoxy-7-prenylaurone (2) were investigated. Both flavonoids, as well as cisplatin as a reference anticancer drug, were tested in vivo against ten human cancer cell lines (breast cancer (MCF-7, SK-BR-3, T47D), colon cancer (HT-29, LoVo, LoVo/Dx), prostate cancer (PC-3, Du145), lung cancer (A549) and leukemia (MV-4-11) and two normal cell lines (human lung microvascular endothelial (HLMEC)) and murine embryonic fibroblasts (BALB/3T3). Chalcone 1 and aurone 2 demonstrated potent to moderate anticancer activity against nine tested cancer cell lines (including drug-resistant ones). The antiproliferative activity of all the tested compounds against cancer and the normal cell lines was compared to determine their selectivity of action. Prenylated flavonoids, especially the semisynthetic derivative of xanthohumol (1), aurone 2, were found as selective antiproliferative agents in most of the used cancer cell lines, whereas the reference drug, cisplatin, acted non-selectively. Our findings suggest that the tested flavonoids can be considered strong potential candidates for further studies in the search for effective anticancer drugs.

Methoxylated derivatives of cinnamic acid play an important role in the formation of the pro-health potential of food products. Numerous reports present them as molecules with strong antimicrobial, antidiabetic, anticancer as well as hepato-, cardio-, and neuroprotective activities. In the last three decades, many research groups have tried to extend the practical application of these molecules as therapeutic and antioxidant agents extensively studying the methods of their lipophilization as the solution of problems of their low oral bioavailability and rapid metabolism. This article summarizes the latest data of natural sources of occurrence, biological potential and bioavailability of methoxy derivatives of cinnamic acids. Metabolism and pharmacokinetics of this group of dietary compounds are also extensively discussed as well as reviewing the methods of their chemical and enzymatic lipophilization in the aspect of their use in food and pharmaceutical industries.

Resveratrol (RES) is gaining recognition as a natural bioactive compound. To expand the possible applications of RES with its enhanced bioactivity as well as to increase the health benefits of long-chain fatty acids, a lipophilization process of RES was performed using three fatty acids: palmitic acid (PA), oleic acid (OA), and conjugated linoleic acid (CLA). The obtained mono-, di-, and tri-esters of RES were evaluated for their anticancer and antioxidant properties against lung carcinoma (A549), colorectal adenocarcinoma (HT29), and pancreatic ductal adenocarcinoma (BxPC3) cell lines. Human fibroblast (BJ) cells were used as a control. Several parameters were investigated: cell viability and apoptosis, including the expression of major pro- and anti-apoptotic markers, as well as the expression of superoxide dismutase, a key enzyme of the body’s antioxidant barrier. Three of the obtained esters: mono-RES-OA, mono-RES-CLA, and tri-RES-PA, which significantly reduced the tumor cell viability up to 23%, at concentrations 25, 10, 50 μg/mL, respectively, turned out to be particularly interesting. The above-mentioned resveratrol derivatives similarly increased the tumor cells’ apoptosis by modifying their caspase activity of pro-apoptotic pathways (p21, p53, and Bax). Moreover, among the mentioned esters, mono-RES-OA induced apoptosis of the analyzed cell lines most strongly, reducing the number of viable cells up to 48% for HT29 cells versus 36% for pure RES. Furthermore, the selected esters exhibited antioxidant properties towards the normal BJ cell line by regulating the expression of major pro-antioxidant genes (superoxide dismutases—SOD1 and SOD2) without the effect on their expression in the tumor, and therefore reducing the defense of cancer cells against increased oxidative stress induced by high ROS accumulation. The obtained results indicate that the esters of RES and long-chain fatty acids allow enhancement of their biological activity. The RES derivatives have the potential for being applied in cancer prevention and treatment, as well as for oxidative stress suppression.

Diabetes mellitus is a worldwide health problem with high rates of mortality and morbidity. Management of diabetes mellitus by dietary components is achievable especially at the initial stage of the disease. Several studies confirmed the antidiabetic activities of simple phenolic acids and lysophosphatidylcholine (LPC). The main goal of this study was to identify new potential insulin secretion modulators obtained by combining the structures of two natural compounds, namely O-methyl derivatives of phenolic acids and phospholipids. LPC and phosphatidylcholine bearing methoxylated aromatic carboxylic acids were tested as potential agents able to improve glucose-stimulated insulin secretion (GSIS) and intracellular calcium mobilization in MIN6 β pancreatic cell line. Our results show that LPC with covalently bonded molecule of p-anisic acid at the sn-1 position was able to induce GSIS and intracellular calcium flux. Notably, 1-anisoyl-2-hydroxy-sn-glycero-3-phosphocholine did not affect the viability of MIN6 cells, suggesting its potential safe use. Furthermore, we have shown that three G protein coupled receptors, namely GPR40, GPR55, and GPR119, are targeted by this LPC derivative.

The development of a biotechnological method for the production of new biologically active phosphatidylcholine containing monoterpene citronellic acid (CA) was the aim of this work. Incorporation of citronellic acid (CA) into egg-yolk phosphatidylcholine (PC) in the lipase-catalyzed acidolysis process was studied. Isoprenoid acid CA was used as an acyl donor and five commercially available immobilized lipases were examined as biocatalysts. The effects of organic solvent, enzyme load, reaction time and molar ratio of substrates on the incorporation of citronellic acid (CA) into the phospholipids were evaluated. Modified phospholipid fraction enriched with CA in the sn-1 position (39% of incorporation) was obtained in high 33% yield using Novozym 435 as biocatalyst. In this study a biotechnological method for production of new phospholipid biopreparation enriched with citronellic acid, which can play an important role as a nutraceutical, was applied.